Specific phobia of amyotrophic lateral sclerosis (ALS phobia) – complex clinical and electromyographic analysis of 120 cases with elements of molecular genetic screening

Specific phobia of amyotrophic lateral sclerosis (ALS phobia) – complex clinical and electromyographic analysis of 120 cases with elements of molecular genetic screening

G.N.LEVITSKY (1,2), A.S.LEVITSKY (3), R.V. CHUB(1), V.M.GILOD (4), E.A.KOVRAZHKINA (5)

Specific phobia of amyotrophic lateral sclerosis (ALS phobia) – complex clinical and electromyographic analysis of 120 cases with elements of molecular genetic screening

1- JSC Clinical and diagnostic center “Real Health” (Moscow)
2- Russian Charity ALS Foundation (Moscow)
3- Private license psychiatrist, narcologist and psychotherapeutist (Moscow)
4- Department of Psychiatry, Eramishantsev Moscow City Hospital (Moscow)
5- Institute of Cerebrovascular disease and Stroke, Russian Scientific Research Medical University

Abstract


We analyzed 120 cases of specific phobia of amyotrophic lateral sclerosis (ALS phobia), 38 males and 82 females within age range 16-48 years (average age 32±11 years). All patients were examined by neurologist, psychiatrist, and then complex needle and stimulation electromyography(EMG/ENMG) was performed, other examinations were performed by patients themselves. In 89,4% patients the wide spectrum of neurological, endocrinological and combined pathology was found, in particular myopathies of various origin, spondylosis and radicular syndromes, polyneuropathies, single and multiple neuropathies, thyroid gland disorders, and in rare cases post-vaccination multiple mononeuropathis, Melkersson-Rosenthal syndrome, celiac disease with secondary systemic carnitine deficiency and acute polytneuromyopathia etc. were found.

We suspected endogenous psychiatric disorders in 11.6%, in whom such specific history and clinical finding were observed such as sensations of twitching around the mouth and in heels, panic attacks and multiple phobias in the past, self-interpretation of (pseudo)atrophies. This subgroup showed strong positive correlation between the duration of phobia and degree by Hamilton Depression Scale (HAM-D) (r=0,59; p=0,028), showed no overt neurological disease assessed either neurologically, or by EMG/ENMG.

We showed that follow-up examination and psychiatric treatment in combination with neurological treatment (atypical neuroleptics, tymoleptics, adaptogenic medications, and rarely antidepressants and hypnotics) allowed to achieve regressive course of phobia in 25% of cases within the average term of 11 months, whereas other patients disappeared from follow up to examine themselves appointing to different neurologists and neurophysiologists and continued to stay in the stay of phobia.

In some patients we performed molecular genetic testing on predilection to shyzotypic disorders, in some of them mutations in correspondent gene or specific polymorphisms were found.

We give recommendations for neurological and psychiatric management of patients with ALS phobia, for how to present them information about differential diagnosis with ALS, neuromuscular and psychiatric disorders.

Introduction


The number of cases of specific phobias of amyotrophic lateral sclerosis (ALS phobia) that we described in our original article in 2012 has recently increased six-fold, which now enables to give a more complete clinical and electromyographic description of this syndrome. Since 2012 in average 33 patients came to JSC CDC Real Health annually, and now we have 120 cases to observe (1).

We should note that the patients require a specific approach due to various neurological, endocrinological and psychiatric symptoms, they are prone to consistently demand the same examinations, such as electromyography, and often annoy attending specialists arousing negative reactions, which deprives them duly consultative and medical aid.

It is obvious that the fear of incurable neurological disease ALS can be accompanied by severe anxiety disorders, which in turn can develop secondary psychopathological addiction (Internet, alcohol, tobacco, drug addiction, etc.) which may increase both anxiety and pathological bodily sensations and hypochondriacal fixation, leading to the development of interpretive delusions, especially in those liable to schizotypal personality disorders (2). ALS phobia is a generalized anxiety disorder with overvalued ideas. The treatment of such patients must include a comprehensive neurological examination, which could reveal the neurological "basis" for the main complaint of the patients (generalized muscle twitching), which may be either systemic symptoms or abnormal bodily sensations induced by increased psychogenic interoception. Psychological and psychiatric care is absolutely required for such patients. It is provided by the authors of this article on a private basis or at the Psychiatric Crisis Resort Department of the Eramishantsev Moscow City Hospital, i.e. outside mental health facilities, so the patients can avoid being registered by psychiatric institutions and, therefore, stigmatization.

This paper is aimed at the comprehensive clinical and electromyographic examination of the neurological and mental status of patients with ALS phobia, sometimes with inclusion of molecular genetic diagnosis elements to reveal the patient’s liability to endogenous mental disorders.

Materials and methods


The study group included 120 patients with ALS phobia, 38 males and 82 females within age range 16-48 years (average age 32±11 years). All patients were examined by neurologist, psychiatrist, and then complex needle and stimulation electromyography (EMG/ENMG) was performed, other examinations were performed by patients themselves. The patient intake included an anamnestic questionnaire for patients with neuromuscular and mental disorders developed by the authors in 2014 (see Table 1). The table also contains patient interviewing results, including retrospective data.

Table 1. Anamnestic questionnaire for patients with neuromuscular and mental disorders


Question Yes No Do not know
Do you feel generalized muscle twitching?
Does the twitching on the right / on the left prevail?
Did you have a temperature before the disease?
Do you have herpetic eruptions?
Do you experience diarrhea after drinking milk?
Do you have celiac disease?
Did you squat?
Do you sometimes feel numbness under the knees?
Have you ever had a general anesthetic?
Did you feel (increased) weakness after a general anesthetic?
Do you have more than 200 g pure alcohol a week?
Do you smoke more than 10 cigarettes a day?
Did travel abroad during the last 6 months?
Do you have pain in the bones?
Do you have twitching in the feet?
Do you have twitching around the mouth?
Do (did) you have alcohol addicts in the family?
Do (did) you have drug addicts in the family?
Do (did) you have gambling addicts in the family?
Do (did) you have relatives with mental disorders?
Are you registered in the mental and/or drug treatment clinic?
Do you have a diagnosed mental disorder?
Have you ever had phobias of other diseases (cancer, multiple sclerosis, etc.)?
Have your lately visited your dentist?
Do you have any chronic infections?
Do you have severe fatigue after exercise?
Have you ever had increased creatinine?
Did you have any vaccinations before the disease?
Do you suffer from diabetes?
Do you have memory loss?
Do you have sleep disorders?
Do you have pains in your stomach?
Is your skin photosensitive?
Did you take hormones?
Do you have a menopause?
Do you have asthma?
Do you have sarcoidosis?
Do you have rheumatoid arthritis?
Do (did) you have cancer?
Are you pregnant?
Do you have pain in your neck and/or waist?
Do you have pain in your pelvis?
Do (did) you have relatives or friends with ALS?
All the patients had anthropometry of limb segments, which was considered normal either when the diameters were equal or when segment diameters of dominant limbs were 1-1.5 cm greater (3). In other cases the diameters were qualified as manifestation of muscle hypotrophy. All the patients underwent needle and stimulation electromyography using the Synapsis electromyograph (Neurotech, Taganrog), including the examination of the most affected muscles according to anthropometric data or visual examination, muscles with twitching sensations, motor and sensory fibers of peripheral nerves (median, elbow, radial, peroneal, posterior tibial, gastrocnemius, musculo-cutaneous, femoral and axillary, in rare cases long thoracic, sublingual, accessory nerves), as well as F-waves (radicular responses) of long nerves of limbs in the projection of affected or "disturbing" limb segments. Usually the examination of deltoid, trapezius muscles, biceps, triceps (once), rectus muscles of thigh, medial and lateral gastrocnemius muscle, tibialis anterior muscles, common finger extensors, in rare cases the first dorsal interosseous muscle, abductor digiti minimi muscles were examined selectively with a 25 mm/0.3 mm2 concentric needle electrode (SLE, the UK). The examinations were conducted according to the relevant methods and regulatory data mentioned in the monograph of S. Oh (2006) (4). The needle examination included an extensive analysis of spontaneous activity and motor unit action potentials (20 to 30), the deviation of the average MUAP duration and amplitude from the norm was calculated according to B.M. Gekht and S.Oh, with analysis of unit variants according to G.N. Levitsky and A.B. Serduk (Table 2) and determination of phases of the denervation-reinnervation process according to B.M. Gekht (4-6).

Table 2. Main combinations of changes in average MUAP duration and amplitude and their interpretation (supplemented)


Changes in MUAP duration and amplitude Possible interpretation
Normal duration and amplitude, without SA Norm
With SA 1. Normal duration, reduced amplitude Neuromuscular junction disorders, central denervation (?)
2. Reduced duration, normal or reduced amplitude (without polyphasy) Denervation of individual muscle fibers without reinnervation, initial denervation changes
3. Normal duration, increased amplitude MUs exchange muscle fibers that are beneficial in terms of reinnervation (neural and/or radicular pattern)
4a. Reduced duration, reduced amplitude (severe polyphasy)
4b. Multiple spontaneous activity of muscle fibers and motor units. Increased amplitude, increased polyphasy, reduced duration
4a. Necrosis of individual muscle fibers (“myopathic pattern”, I and II stage EMG/DRP);
4b. “Myositic pattern”.
5. Reduced duration, increased amplitude (slight polyphasy) Reinnervation of a small number of denervated muscle fibers with MU reconstruction in the form of compact bundles (I and II stage DRP) (expanded neural pattern)
6. Increased duration, increased amplitude (moderate polyphasy) Reinnervation of a great number of denervated muscle fibers with MU reconstruction in the form of compact bundles (III-V stage DRP) (neural and neuronal/pseudoneuronal pattern)
7. Normal/reduced amplitude, increased duration (severe polyphasy) Demyeliniation
Psychological and psychiatric consultation with the assessment of patients using the Hamilton Depression Scale (HAM-D) was carried out either at Real Health CDC by invited private psychiatrist practitioner, narcologist and psychotherapist A.S.Levitsky or at the Psychiatric Crisis Resort Department of the Eramishantsev Moscow City Hospital (headed by V.M.Gilod, candidate of medical sciences) (7). The diagnosis of mental disorders was determined in accordance with the ICD-10.

The patients were selectively examined for genes that, according to the literature, predispose to alcohol addiction and shyzotypic disorders, i.e. the dopamine active transporter 1 gene (DAT1), the kappa opioid receptor gene (OPRK1), the mu opioid receptor (OPRM1), the catechol-O-methyl transferase (COMT), the ankyrin repeat and kinase domain containing 1 (ANKK1), the dopamine D4 receptor (DRD4), the monoamine oxidase A (MAO-A). The study was conducted on the basis of the Centre for Molecular Genetics LLC (the laboratory is headed by professor A.V. Polyakov) (8-12).

An ALS comparative analysis was carried out as part of the clinical and electromyographic examination. None of the patients were diagnosed with ALS according to the Revised El Escorial Criteria, neither at the screening nor in 25% cases of the repeated follow-up study, nor in other cases when the patients were interviewed by telephone 1 or 2 years later (13).

On a selective basis, according to recommendations of our team or before visiting the clinic, the patients underwent thyroid ultrasound and hormone blood tests, transcranial magnetic stimulation (TMS), tests for somatosensory, visual and other evoked potentials, sympathetic skin response, electroencephalography, magnetic resonance imaging of the brain, cervical, thoracic and lumbar spine, shoulder joints, ultrasound of the abdomen, pelvis, peripheral nerves and muscles, esophagogastroduodenoscopy, colonoscopy, computed tomography of the brain, mediastinum, ECG, echocardiogram, Doppler and transcranial Doppler ultrasound of main arteries of the head, complete blood count and biochemical blood tests for vitamins, parathyroid hormone, immunoglobulin G and M, herpes viruses 1, 2, 6, 7, the Epstein-Barr virus, cytomegalovirus, Yersinia, Borrelia, Chlamydiae, mycoplasma, etc.

Statistical processing was performed using the BIOSTAT statistical software (Hungary, 1998). Student's t-test was used for parametrically distributed indicators, Spearman's rank correlation coefficient was calculated. Difference were considered statistically significant at р<0,05.

Results


As a result of the study the patients with ALS phobia were diagnosed with the following neurologic, psychiatric and endocrine disorders (Table 3).

Table 3. Neurologic and psychiatric diagnoses of patients with ALS phobia


Diagnoses Number of patients, n (%)
Signs of moderate and/or maximum MUAP amplitude increase 43 (35.8%)
Radiculopathies 9%
Tunnel mononeuropathies 11 (9.2%)
Multiple tunnel mononeuropathies 15 (12.5%)
Multiple radiculopathies 6 (5%)
Polyneuropathies (including Charcot-Marie-Tooth hereditary neuropathy, toxic, diabetic neuropathies) 3 (2.5%)
Multiple mononeuropathies, including MMN with conduction block, Melkersson-Rosenthal syndrome, consequences of post-vaccination neuropathy 5 (4.2%)
Myelopathy 2 (1.6%)
Borreliosis 1 (0.8%)
Yersiniosis 1 (0.8%)
Multiple myositis 2 (1.6%)
Hereditary myopathies 3 (2.5%)
Metabolic myopathies 9 (7.5%)
- statin-induced 2 (1.6%)
- steroid-induced 2 (1.6%)
- thyroid-induced 5 (4.2%)
Parsonnage-Turner syndromе 3 (2.5%)
Mitochondrial disorders 1 (0.8%)
Trichinellosis 1 (0.8%)
Celiac disease with secondary systemic carnitine deficiency and acute polyneuromyopathy 1 (0.8%)
Hypothyreosis 6 (5%)
Iatrogenesis 1 (0.8%)
No ENMG pathology 35 (29.1%)
Mental disorders 14 (11.6%)
- hysteria 2 (1.6%)
- schizophrenia 3 (2.5%)
- schizoaffective disorder 1 (0.8%)
- schizotypal personality disorder 14 (11.6%)
– bipolar disorder 1 (0.8%)

*According to Table 2, this sign can be explained by irritation of the peripheral nerve root. However, many patients showed non-myotonic psychogenic disorders of muscle relaxation in the form of voluntary muscle tension, which “simulated” spontaneous activity. Differences of this phenomenon from the true spontaneous activity are presented in Example 8. We believe that in some cases the MUAP amplitude increase can be induced by increase in the muscle tension and, therefore, some of the patients can be qualified as “no EMG pathology”.

The average duration of phobic symptoms was 20.2 ± 12.3 months, the average HAM-D score was 13.5 ± 10.7. Patients with specific symptoms of ALS phobia, such as psychiatric disorder and other phobias in history, perioral twitching, heel twitching and patients who took physiological curves of the body for atrophies showed the average HAM-D score of 21.2±5.3 with the average duration of the phobia of 25.8±16.4 months. This group of patient had a positive significant correlation of phobia duration and the HAM-D score (r=0.59; p=0.028) (see Figure 1). Other patients did not show this correlation.

Figure 1. Positive significant correlation of phobia duration and the HAM-D score in patients with specific symptoms of ALS phobia. 

fig03.jpg
  
Patients diagnosed with schizophrenia and shyzotypic disorder in 7 cases showed deletion and in 1 case insertion in the DAT1 gene and abnormal polymorphisms in the OPRK1, OPRM1, COMT, ANKK1, MAO-A genes, but no insertion or deletion in the DRD4 gene. The patient diagnosed with bipolar disorder had blood tests for mutations in the GSR3-β gene, but no mutations characteristic to this pathology, i.e. duplication in exon 9 of the gene, were revealed (12).

We believe that it would be very illustrative to give some examples of patients with ALS phobia, causative neurological symptoms, with the needle and stimulation electromyography picture and revealed abnormal polymorphisms and mutations.

Example 1. ALS phobia and schizotypal personality disorder (1).


Patient A.-A. I.N., 34 years old.

Complaints: since May 2014 has frequent yawning, shallow breathing, tachycardia 95-100 hbm, weakness and drowsiness, diagnosed with vegetative-vascular dystonia, was administered coraxan, riboxin, panangin. In summer she went in for sports, but tachycardia was not resolved. Took coraxan for three months. In September, she fainted in the subway, this aroused concern about her health and tachycardia recurred. She was administered zoloft (took only one tablet) and betaloc zok. BP dropped to below 90/60, pulse – to 80-90. She began to fear suffocation. The sleep became restless and was not satisfying, she became drowsy during the day, the ability to work decreased. A week ago, she had to prepare for state exams. She noticed twitching of the left eye, then the twitching spread over the body. She began to read about ALS in the Internet, after that the twitching increased, aching pain appeared in her calves, hips, she began to feel fatigue in her legs. She took pantocalcin, phenazepam (severe drowsiness), strеsam for 1 months, the administration of eglonil resulted in breast growth (increased prolactin); she took teraligen for two weeks (severe drowsiness), ladasten, B12 vitamin, kudesan and carnitine. She noticed pain in the lower back after exercises

At the age of 18 to 23, she studied the ecology in the Forestry Academy. She gave birth to a child when she was 25, divorced. Her husband reproached her for “worthlessness”, found another woman, a wealthy one. The patient had stress caused, among other, by the fact that she had to raise a sick child. The patient felt guilty had she had failed to preserve the family. She always try to be calm, keep emotions away. When she was 27, she entered the Medical College for a medical assistant. The patient’s daughter was under the care of the patient’s mother. Then she got married and divorced again two years ago. She took it very emotional. The patient’s second husband had hypochondria, including chronic prostatitis, and he believed that his wife failed to cope with his treatment, although she made much efforts.

The patient was examined. Viral myocarditis was excluded due to monomorphic ventricular arrhythmia, according to the heart MRI. Thyroid ultrasound, CBA and the blood biochemistry were in norm, with a slight increase in pancreatic amylase (due to excessive medication treatment), cortisone was 1.5 times above the norm. She suffers from gastroesophageal reflux disease, biliary dyskinesia, sliding hiatal hernia, 2 erosions in the esophagus, was treated with ultop, almagel. Brain MRI – no pathology in 2013 and 2014, the circle of Willis is open (lack of the two posterior communicating arteries) Thyroid ultrasound – no pathology. The neck X-ray shows a slight semiluxation of the atlas to the left (explained by accelerated labor), thoracic spine scoliosis, early signs of degenerative disc disease of the cervical and thoracic spine.

The patient’s grandfather (on the paternal side) had 2 hemorrhagic strokes. Now he is 87, no paralysis. Her grandmother (on the maternal side) had ischemic stroke, she died at the age of 91, seven years after the stroke. The patient’s mother has hypertension, suffered from Werlhof's disease (thrombocytopenia), which was cured. The patient’s father does not have any health problems. The patient’ s daughter is 8. She suffers from anxiety disorder, compulsive movement disorder, severe sleep disorders with phobias and bronchial obstruction, sleeptalking, no diagnosis, the EEG is normal, no vocal or motor habit spasms, mentally well developed, eats very little, weighs 18.5 kg at the age of 8.

In the neurological status there are no cerebral, meningeal or cognitive disorders, cranial nerve disorders. No paresis, the muscle tone is normal, tendon reflexes are normal in arms and increased in legs, no pathological reflexes. No atrophies and fasciculations. Anthropometric results: the right and left shoulders are 23 cm each, the left and right forearms are 21 cm each, the right thigh is 45 cm, the left thigh is 44 cm, the right lower leg is 34 cm, the left lower leg is 32 cm (possible slight hypotrophy of the left leg). Sensitivity and co-ordination are normal. Movements in the spine cord are painless. Right thoracic scoliosis, stage 1.

Needle electromyography


In deltoideus sin. (C5-6) spontaneous activity (SA) is not revealed. Average MUAP duration 10.9 ms with the norm of 10.7 ms – increased by 2% (with the norm of +/-13%). Average MUAP amplitude 631 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 1443 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 70% (the norm is up to 25%). The recruitment pattern is normal. Normal MUAPs with increased polyphasy, neural MUAPs. Possible radicular involvement. In m. Vastus lateralis (L2-4) on the left no SA revealed. Average MUAP duration 10.26 ms with the norm of 11 ms – decreased by 7% (with the norm of +/-13%). Average MUAP amplitude 979 μV (increased, with the norm of 300-850 μV), the maximum MUAP amplitude is 2219 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 70% (increased, the norm is up to 15%). The recruitment pattern is normal. Possible radicular involvement.

In m. Tibialis anterior (L5-S1) on the left SA is in the form of 1 fasciculation potential. Average MUAP duration 10.42 ms with the norm of 11 ms – decreased by 5% (with the norm of +/-13%). Average MUAP amplitude 949 μV (increased, with the norm of 300-850 μV), the maximum MUAP amplitude is 2444 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 70% (the norm is up to 25%). The recruitment pattern is normal. Possible radicular involvement.

Stimulation ENMG


Amplitude of M-response n. peroneus sin. 13.2 mV (the norm is above 3.5 mV). Distal latency of M-response 5.2 ms (normal less than 6.2 ms). Residual latency 3.82 ms (increased, with the norm of up to 3 ms) No conduction block. Nerve conduction velocity in the lower leg – 43.6 m/s (the norm is above 40 m/s), in the fibular channel – 88.9 m/s (normal). F-responses – NCV range 47-43 m/s (the norm is above 30 m/s), dropouts 14/20, no giant responses, no repeated ones, polyphasic – 1. Amplitude of M-response n. peroneus dext. 15.2 mV (normal). Distal latency of M-response 3.85 ms (normal less than 6.2 ms). RL 2.77 ms (the norm is up to 3 ms). NCV in the lower leg – 46.2 m/s (the norm is above 40 m/s), in the fibular channel – 30.3 m/s (normal).

Hamilton Depression Scale – 18 scores (severe generalized anxiety disorder)

Diagnosis – severe generalized anxiety disorder with overvalued ideas. ALS phobia. No ALS confirming data. Osteochondrosis of the cervical, thoracic and lumbar spine. Radiculopathy of roots forming the left peroneal nerve, fibular tunnel syndrome of the right peroneal nerve

Recommendations:


1. MRI of the lumbar, cervical and thoracic spine.
2. Seroquel 100 mg, at night, 1 hour before meal, for 3 months
3. Depakine chrono 500 mg 1-1\2 2 times a day. 3 months supervision using the Hamilton Depression Scale
4. Phenibut 250 mg, 1 tablet 3 times a day, for 2-3 months
5. Psychotherapy
6. Consultation of the patient’s daughter by a child psychiatrist
7. Genetic analysis for the DAT, DRD4, OPRK, OPRM1, ANKK1 genes
8. Texamen 2.0, i.m. No. 5
9. Planterotherapy
10. Posture corrector, soft
11. Phonophoresis with hydrocortisone No. 6 to the right fibular channel (tunnel syndromes of the peroneal nerve)

After additional MRI examination of the cervical and lumbar spine: slide protrusions of the С4-6, L3-5 discs up to 2 mm, L5-S1 up to 3.5 mm with left-sided foraminal compression which is consistent with EMG data.

Molecular genetic testing and genetic screening.


DNA analysis results:

DNA sample number
ANKK1
c.2137G>A A/G
OPRM1
c.118A>G A/A
COMT
c.472G>A G/A
OPRK1
c.258-4707A>G A/G
DRD4
(48bp repeat) 4/4
DAT1
c.*948_*987del40
A141 Alarcon Avilla I.N. (patient) N/ins

Conclusion: heterozygous insertion in the DAT1 gene, heterozygous replacement c.2137G>A in the ANKK1 gene, which predisposes to schizotypal personality disorder.

Note: deletion corresponds to sequence 9, insertion – to sequence 11.

The patient refused further observation and treatment.

Example 2. ALS phobia and schizotypal personality disorder (2).


Patient A.A.L., 44 years old, complained of generalized muscle twitching in January 2013, filmed the twitching, complained of not only in arms and legs, but also in the feet, around the mouth, noted “swallowing disorders”. Needle EMG does not show spontaneous activity, MUAP moderate and maximum amplitudes are slightly increased, the duration is normal, polyphasy is slightly increased (the deltoid muscle, common finger extensor, rectus muscles of thigh and tibialis anterior muscle were examined). HAM-D scores is 25 points. No pathology in the neurological status. The patient was explained that the filmed muscle twitching was so-called benign myokymia. As for the personal characteristic of the patient, it should be note that he holds high public office and is a successful businessman, comes from a poor incomplete family. He has medical and economic (as the second) university degree. The patient had a distant relative who died of ALS. Despite the high level of anxiety, he is not aggressive, friendly, disposed to further consultation and treatment.

He came again in February 2015, complaining of twitching in the triceps after paying tennis. The examination revealed fasciculations in the left triceps, pain in the neck. No other pathologies were revealed. Myography results are presented below.

Needle electromyography



In m. Biceps brachii dext. (C4-6) spontaneous activity (SA) is not revealed. Average MUAP duration 11.33 ms with the norm of 11.2 ms – increased by 1,1% (with the norm of +/-13%). Average MUAP amplitude 644 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 1100 μV (the norm is up to 1200 μV). Polyphasic MUAPs 5% (the norm is up to 5%). The recruitment pattern is normal. No pathologies revealed.

In m. Triceps brachii sin. (C4-6) SA in the form of 2 potentials of positive sharp waves and 5 fibrillation potentials. Average MUAP duration 10.03 ms with the norm of 11.7 ms – decreased by 14% (with the norm of +/-13%). Average MUAP amplitude 458 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 1044 μV (the norm is up to 1200 μV). Polyphasic MUAPs 25% (increased, the norm is up to 5%). The recruitment pattern is normal. Stage 1 denervation-reinnervation process (DRP), acute denervation, probably of radicular genesis, are revealed. Normal neural initial, demyelinating MUAPs.

Stimulation ENMG


Amplitude of M-response in n. radialis dext. 2.06 and 1.06 mV (reduced, the norm is above 2.5 mV for the abductor digiti minimi muscle). Distal latency of M-response 3.45 ms (increased, normal less than 2.5 ms). RL 2.46 ms (increased, with the norm of up to 1,5 ms) No conduction block. M-responses have axonal alterations. NCV in the forearm – spiral channel 70.7 m/s (the norm is above 50 m/s). No F-responses obtained.

Conclusion: Acute radiculopathy of roots forming the left radial nerve with axonopathy and acute denervation in the needle EMG. Generalized anxiety disorder with overvalued ideas. ALS phobia. No ALS confirming data.

Consultation of the neurologist and comments - according to the patient, a recent MRI of the cervical spine revealed a disc protrusion with a right-sided foraminal component (documents are not presented). Recommendations: Texamen 2.0 i.m. No. 5, then texamen 20 mg in the morning before meal for 7 days, physiotherapy – electrophoresis with magnesium sulfate to the С6-7 region on the left No. 6, avoid heavy lifting by the left shoulder joint, load on the cervical spine, including sports. Control EMG and EMG 2 weeks after the start of treatment.

Examination of the DAT1, ANKK1, OPRM1, COMT, OPRK1, DRD4, GSK3B genes

DAT1
c.*948_*987del40 N/DEL
ANKK1
c.2137G>A G/G
OPRM1
c.118A>G A/A
COMT
c.472G>A A/A
OPRK1 c.258-4707A>G A/A DRD4
(48bp reapeat) 2/4
PM-associated GSK3B gene
c.-1001T>C, rs334558 T/T
GSK3B gene, 1-12 exons N/N

Genetic screening: Heterozygous deletion in the DAT1 gene, significantly predisposing to schizotypal disorders. Homozygous polymorphism in the COMT gene, which can predispose to schizotypal disorders according to individual authors. No pathologies in the ANKK1, OPRM1, OPRK1, DRD4 genes. Normal polymorphism in the GSK3B gene in the promotor area, no mutations in the gene, no disposition to bipolar disorder according to the examination results (14).

Currently the patient continues periodic examinations – he underwent macro electromyography abroad, repeated needle myography in Moscow and St. Petersburg, genetic examinations for mutations in the androgen receptor (spinal and bulbar muscular atrophy), no mutations have been identified, screened for mutations in all known ALS genes. No mutations revealed. He stopped to take psychotropic drugs a month after the initial consolation and did not start again.

Example 3. ALS phobia and multifocal motor neuropathy with conduction blocks (1).


Complaints of visible twitching in the calf muscles for a week. The patient under went a surgery in the lumbar spine for hernia. After a repeated MRI – adhesion is suspected. When twitching appeared, the patient began to study ALS information in the Internet. The patient also has a long history of pain in the neck. Her mother suffers from rheumatoid arthritis. In addition, the patient had regredientny humeroscapular periarthrosis. Mental illness, drug and alcohol addition, epilepsy were not noted in the family.

In the neurological status there are no cerebral, meningeal or cognitive disorders, cranial nerve disorders. Anxiety. EMG was carried out after administration of 2 ml of 2.5% phenazepam. No paresis, the muscle tone is normal, tendon reflexes are normal in arms and reduced in legs, especially in the Achilles tendons, no pathological reflexes. Atrophy of short foot extensors, fasciculations in the calf muscles. Sensitivity and co-ordination are normal. Movements in the spine cord are painless.

Needle electromyography


In deltoideus dext. (C5-6) spontaneous activity (SA) is not revealed. Average MUAP duration 10.24 ms with the norm of 11.1 ms – increased by 7,8% (with the norm of +/-13%). Average MUAP amplitude 499 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 705 μV (the norm is up to 1200 μV). Polyphasic MUAP 10% (the norm is up to 25%). The recruitment pattern is normal. No pathology revealed.

In m. Extensor digitorum communis dext. (C4-6) SA is not revealed. Average MUAP duration 9.18 ms with the norm of 10.5 ms – increased by 12,6% (with the norm of +/-13%). Average MUAP amplitude 427 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 825 μV (the norm is up to 1200 μV). Polyphasic MUAP 15% (the norm is up to 15%). The recruitment pattern is normal. No pathology revealed.

In m. Vastus lateralis (L2-4) no SA on the right. Average MUAP duration 11.1 ms with the norm of 12 ms – reduced by 7,8% (with the norm of +/-13%). Average MUAP amplitude 832 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 2282 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 45% (increased, the norm is up to 15%). The recruitment pattern is normal. Possible radicular involvement.

In m. Tibialis anterior no SA on the right (L4-S1). Average MUAP duration 12.72 ms with the norm of 11.8 ms – increased by 7,7% (with the norm of +/-13%). Average MUAP amplitude 657 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 900 μV (the norm is up to 1200 μV). Polyphasic MUAP 100% (the norm is up to 25%). The recruitment pattern is normal. Possible radicular involvement in the form of demyelination signs, which correlates with increased duration of M-responses from the peroneal nerve on the foot.

In m. Gastrocnemuis lateralis on the right (L5-S1) SA in the form of 5 fasciculations potentials, 7 fibrillation potentials, 2 positive sharp waves. Average MUAP duration 12.72 ms with the norm of 11.8 ms – increased by 37,8% (with the norm of +/-13%). Average MUAP amplitude 777 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 1952 μV (in 3 MUAPs, the norm is up to 1200 μV). Polyphasic MUAP 85% (increased, the norm is up to 25%). The recruitment pattern is reduced. IV stage DRP with active denervation and reinnervation.

Figure 2. Fasciculations and fibrillation in the gastrocnemius muscle.

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Figure 3. Conduction block in the posterior tibial nerve (according to Chaundry et al., 1994) (15).

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Stimulation ENMG


Amplitude of M-response n. peroneus sin. 6.53 mV (the norm is above 3.5 mV). Distal latency of M-response 4.6 ms (normal less than 6.2 ms). Residual latency 3.31 ms (increased, with the norm of up to 3 ms) No conduction block. NCV in the lower leg – 30.9 m/s (the norm is above 40 m/s), in the fibular channel – 65.4 m/s (normal). F-responses – NCV range 51-52 m/s (the norm is above 30 m/s), dropouts 3/20, no giant responses, repeated – 7, polyphasic – 7.

Amplitude of M-response n. peroneus dext. 0.32 mV, 0.83, 0.87 mV (sharply reduced). Distal latency of M-response 6.62 ms (increased, normal less than 6.2 ms). RL 4.78 ms (increased, the norm is up to 3 ms). Duration of the 2nd and 3rd responses is increased to 12-14 ms. NCV in the lower leg – 32.5 m/s (the norm is above 40 m/s), in the fibular channel – 25 m/s (reduced with inversion). F-responses – NCV range 54-62 m/s (the norm is above 30 m/s), dropouts 3/20, no giant responses, repeated – 1, polyphasic – 0.

The amplitude of M-response at the stimulation of the left posterior tibial nerve is 12.6 mV (normal, the norm is above 3.5 mV). Response duration – 15 ms. Amplitude of the proximal response 5.2 mV, duration 9.35 ms (complete conduction block). NCV 31.2 ms (reduced, the norm is above 40 ms). DL 4.6 ms (the norm is below 6.3 ms), RL 1.72 ms

The amplitude of M-response at the stimulation of the right posterior tibial nerve is 17.9 mV (the norm is above 3.5 mV). DL 4.75 ms (the norm is below 6.2 ms), RL 2.85 ms (the norm is below 3 ms). NCV 42.2 ms (the norm is above 40 m/s). Complete conduction block in the lower leg, proximal amplitude 7.56 mV, distal response duration 13.25 ms, proximal response duration – 10.12 ms (less that 115% of the distal one)

ENMG report: conduction blocks in posterior tibial nerves correlating with active denervation and reinnervation with pseudoneuronal distribution of the MUAP histogram in the right lateral gastrocnemius muscle, with innervation in the muscle of the same segment (no spontaneous activity in the right tibialis anterior muscle, slight radicular involvement, which is impossible for ALS), no pathology in the right shoulder and forearm muscles, no spontaneous activity, as well as in the muscle of the right thigh, where slight radicular involvement is revealed; radiculopathy of roots forming the right peroneal nerve with axonopathy and secondary demyelination, fibular tunnel syndrome of the right peroneal nerve, irritation of roots of the left peroneal nerve.

Diagnosis – generalized anxiety disorder with overvalued ideas. ALS phobia. No ALS confirming data. Osteochondrosis of the cervical and lumbar spine. Effects of surgery in the lumbar spine. Radiculopathy of roots forming the right peroneal nerve, fibular tunnel syndrome of the right peroneal nerve, irritation of roots of the left peroneal nerve. Multifocal motor neuropathy with conduction blocks?

Recommendations:


1. MRI of the lumbar spine
2. Transcranial magnetic stimulation - blood test for coagulation profile - activated partial thromboplastin time, prothrombin ratio, international normalisation ratio, prothrombin (the patient suffers from increased bleeding) and creatine phosphokinase
3. The blood test for antibodies to gangliosides, regardless of the result – treatment with octagam 0.2 g/kg of body weight per day (10 grams per day) with 400 ml of saline intravenously for 4 days with (possibly) 2.5 mg of warfarin under with coagulation monitoring and INR before and after the course in the day patient department, ex iuvantibus with EMG and ENMG monitoring after treatment
4. Alternatively, cyclophosphamide 70 mg per day supported by gastroprotectors, dicynon.
5. Seroquel 25 mg at night for 5 days, then 50 mg at night for 5 days, then 100 mg at night 1 hour before meal, for 3 months
6. Depakine chrono 500 mg 1\2 2 times a day. for 3 months
7. Phenibut 250 mg, 1 tablet 3 times a day, for 3 months
8. Psychotherapy
9. Texamen 2.0, i.m. No. 5
10. Planterotherapy
11. Electrophoresis with caripazim No. 20 to the lumbar spine, electrophoresis with hydrocortisone No. 6 to the right fibular channel (tunnel syndromes of the peroneal nerve).

The TMS did not reveal any pathologies, but revealed positive antibodies to GM1 gangliosides, which can confirm the diagnosis. The cancer search screening program was additionally recommended.

Subsequently, the patient made many calls to the clinic and to the personal phone of the consultant, she was extremely anxious. She was further proposed to have the analysis for genetics of bipolar disorder and schizotypal. She did not come again. Later, she was identified as a patient forum user, where she wrote that she had visited another specialist, who had not confirm conduction blocks and called our conclusion “absurd”. After repeated visiting the specialist he diagnosed “crampy fasciculation syndrome in the calf muscles, no data confirming a motor neuron disease”. The patient participated in the cancer search screening program, which did not reveal any pathologies. She intends to be examined for infections, visited another electromyography specialist, who confirmed conduction block in one of the posterior tibial nerves.

Example 4. ALS phobia and multifocal motor neuropathy with conduction blocks (2).


A.D.A., 34 years old

Complaints of twitching, especially in the calf muscles, arms, body for 3 weeks. Weakness, intolerance to physical activity, tension of the face since 2009. In 2007, he consulted about stretch marks on the thighs, in the axillary region from 2010, increased cortisone level was not detected by laboratory methods, he did not have consultations of endocrinologist. Before the twitching appeared, he had increased body temperation up to 37.8C (immedicately before the fasciculations), after the temperature increase he was vaccinated with tetanus toxoid in connection with a scratch inflicted by a cat (before fasciculations). In 2013, the level of gamma globulins was slightly increases to 13.6, with the norm of 13.5. Test for APK was not conducted. Test for borreliosis was negative. In 2014, he had a slight increase in albumin – 50 (the the norm of 47), reduction of creatinine – 76 (with the norm of above 80), however, gamma-globulins were not increased.

The patient was examined – the stimulation ENMG did not reveal significato pathology, the needle EMG revealed reduced average MUAP amplitude, sporadic fasciculation potentials. Blood tests revealed increased cholesterol, triglycerides, LDL and HDL were not increased, calcium was slightly increased to 2.57, adrenocorticotropic hormone was slightly increased to 53 (with the norm of 46), the CBC revealed mild neutropenia and lymphocytosis.

In the neurological status there are no cerebral, meningeal or cognitive disorders, cranial nerve disorders. No paresis, the muscle tone is normal, tendon reflexes in arms and knees are vivid, ankle jerks are of average vivacity, there are patholodical Rossolimo reflexes in hands and feet. No atrophies. Anthropometric results: right shoulder 29 cm, left shoulder 29 cm, right forearm 25 cm, left forearm 23 cm, the right and left thigh are 47 cm each, the right and left lower legs are 35 cm each, fasciculations in the calf muscles. Hypalgesia in the right shoulder region, the coordination is normal. Movements in the spine cord are painless.

Needle electromyography



In m. Tibialis anterior on the right (L4-S1) no spontaneous activity (SA) is revealed. Average MUAP duration 13.89 ms with the norm of 11.4 ms – increased by 21,4% (with the norm of +/-13%). Average MUAP amplitude 1175 μV (increased, with the norm of 300-850 μV), the maximum MUAP amplitude is 3195 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 50% (the norm is up to 25%). The recruitment pattern is normal. IV stage DRP.

In m. Gastrocnemuis lateralis on the right (L5-S1) SA in the form of 1 fasciculation potential, 5 fibrillation potential, 1 positive sharp wave. Average MUAP duration 12.72 ms with the norm of 10.2 ms – increased by 34% (with the norm of +/-13%). Average MUAP amplitude 999 μV (increased, with the norm of 300-850 μV), the maximum MUAP amplitude is 2989 μV (increased, the norm is up to 1200 μV). Polyphasic MUAP 25% (increased, the norm is up to 25%). The recruitment pattern is reduced. IV stage DRP with active denervation and reinnervation.

In m. Gastrocnemuis lateralis on the left (L5-S1) SA in the form of 1 fasciculation potential. Average MUAP duration 12.72 ms with the norm of 11.8 ms – increased by 33,4% (with the norm of +/-13%). Average MUAP amplitude 610 μV (with the norm of 300-850 μV), the maximum MUAP amplitude is 1193 μV (the norm is up to 1200 μV). There are some demyelinating MUAPs. Polyphasic MUAP 35% (increased, the norm is up to 25%). The recruitment pattern is reduced. IV stage DRP.

Stimulation ENMG


Amplitude of M-response n. peroneus sin. 16.6 mV (the norm is above 3.5 mV). Distal latency of M-response 4.05 ms (normal less than 6.2 ms). Residual latency 2.73 ms (the norm is up to 3 ms) No conduction block. Nerve conduction velocity in the lower leg – 43.6 m/s (the norm is above 40 m/s), in the fibular channel – 59.5 m/s (normal). F-responses – NCV range 53-24 m/s (the norm is above 30 m/s), dropouts 4/20, no giant responses, repeated – 2, polyphasic – 1.

Amplitude of M-response in n. peroneus dext. 25.3 mV (normal). Distal latency of M-response 2.8 ms (normal less than 6.2 ms). RL 1.64 ms (the norm is up to 3 ms). NCV in the lower leg – 42 m/s (the norm is above 40 m/s), in the fibular channel – 53.3 m/s (normal). F-responses – NCV range 48-52 m/s (the norm is above 30 m/s), dropouts 2/20, no giant responses, repeated – 1, polyphasic – 0.

The amplitude of M-response at the stimulation of the right posterior tibial nerve is 27.3 mV (normal, the norm is above 3.5 mV). Response duration – 113 ms Amplitude of the proximal response 11.4 mV, duration 16.3 ms (partial conduction block). NCV 42.6 ms (the norm is above 40 m/s). DL 4.05 ms (the norm is at least 6.3 ms), RL 1.94 ms F-responses – NCV range 38-73 m/s (the norm is above 30 m/s), no dropouts, no giant responses, repeated – 8, 4 responses lost normal polyphasy, A-responses - 2.

The amplitude of M-response at the stimulation of the left posterior tibial nerve is 21.7 mV (the norm is above 3.5 mV). DL 3.9 ms (the norm is below 6.2 ms), RL 1.79 ms (the norm is below 3 ms). NCV 42.6 ms (the norm is above 40 m/s). No conduction blocks. Proximal amplitude 18.9 mV. F-responses – NCV range 49-54 m/s (the norm is above 30 m/s), no dropouts, no giant responses, repeated – 11, polyphasic – 0 A-responses – 3

Amplitude of sensor activity potential n. suralis sin. 14.8 μV (the norm is above 6 μV), NCV – 39.9 m/s (slightly reduced, the norm is above 40 m/s).

Amplitude of sensor activity potential n. suralis dext. 21.8 мкВ (normal), RC - 43 m/s (normalO Amplitude of M-response n. ulnaris dext. 13.3 mV (the norm is above 6.0 mV). Distal latency of M-response 2.65 ms (increased, normal less than 3.3 ms). RL 0.81 ms (the norm is below 2.5 ms) No conduction blocks. NCV in the forearm – spiral channel 48.9 m/s (the norm is above 50 m/s), in the cubital channel – 53.1 m/s (normal)

ENMG report: partial conduction block in the right posterior tibial nerve correlating with active denervation and reinnervation with pseudoneuronal distribution of the MUAP histogram in the right lateral gastrocnemius muscle, with innervation in the muscle of the same segment (no spontaneous activity in the right tibialis anterior muscle, increased MUAP duration and amplitude, with is not consistent with ALS), increased MUAP duration and amplitude in the left gastrocnemius muscle, but spontaneous activity includes 1 fasciculation potential. No agitation and conduction pathologies in the peroneal nerve, other than the conduction block in the peroneal nerve root on the left. Gastrocnemius (sensory) nerves are not affected. Motor fibers of the right ulnar nerve are not affected.

Diagnosis: Multifocal motor neuropathy with conduction blocks on the onset (?) based on the revealed partial conduction block in the right posterior tibial nerve, with signs of denervation and reinnervation only in the right lateral gastrocnemius muscle and, possibly, at the root level of the left peroneal nerve, without destruction of sensory nerves, without distinct signs of pyramidal insufficiency (increased arm and knee reflexes and bilateral mild pathological signs can correlate with autonomic dysfunction), clinical fasciculations in gastrocnemius muscles without atrophy, transient increase of gamma-globulins in history. Generalized anxiety disorder with overvalued ideas. ALS phobia. No ALS confirming data. Osteochondrosis of the lumbar spine.

Recommendations:


1. MRI of the lumbar spine, brain
2. Transcranial magnetic stimulation - Kovrazhkina Elena Anatolyevna, candidate of medical sciences, 89057285911
3. Blood analysis for CPK
4. The blood test for antibodies to gangliosides, regardless of the result – treatment with octagam 0.2 g/kg of body weight per day (18 grams per day) with 400 ml of saline intravenously for a week with 2.5 mg of warfarin under with coagulation monitoring and INR before and after the course in the day patient department, ex iuvantibus with EMG and ENMG monitoring after treatment
5. Seroquel 25 mg, at night, 1 hour before meal, for 2 months
6. Depakine chrono 500 mg 1\2 2 times a day. for 2 months
7. Phenibut 250 mg, 1 tablet 3 times a day, for 2 months
8. Examination of the DRD4, DAT1, OPRK1, OPRM1, COMT, ANKK1 anxiety disorder genes

Transcranial magnetic stimulation (TMS) revealed no pathology and confirmed the "vegetative" character of increased reflexes. Antibodies to GM1 gangliosides and other gangliosides are not revealed. Pathologies in genes proposed for examination are not revealed.

After octagam infusion the conduction block disappeared in one posterior tibial nerves (Figure 4), but appeared again 2 months later (Figure 5).

Fig. 4. Conduction block regression.

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Nerve Current, mA Distance, cm NCV, m/s lat., ms res. lat., ms Ampl., mV dlt., ms Area, mV*ms Phases
Tibialis D ср.40,59
Inner malleolus 50 10 4.2 1.74 23.91 14.58 61.61 2
Popliteal fossa 50 51 40.59 14.3 13.89 12.35 42.56 2

Figure 5. Conduction block recurring.

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Nerve Current, mA Distance, cm NCV, m/s lat., ms res. lat., ms Ampl., mV dlt., ms Area, mV*ms Phases
Tibialis D ср.43,9
Inner malleolus 40 9 4.6 2.55 23.3 13.62 55.72 4
Popliteal fossa 100 54 43.9 14.85 2.69 8.95 8.11

Figure 6. Conduction block in the needle EMG – dominating primary denervation and demyelinating unit in one of the points.

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The patient refused to take repeated infusion of octagam. He was proposed cyclophosphamide treatment – pulse therapy and tablets. At present, the patient is deciding on this matter. A third party consultant did not confirm the conduction block.

Example 5. ALS phobia and suspected neuromyotonia (Isaacs' syndrome).


Patient Sh.A.N., 28 years old, complains of twitching in the gastrocnemius muscles for a year and intrusive thoughts of ALS with sleep disorder.

In the neurological status, the following was revealed: vivid tendon reflexes, Rossolimo’s and Jakobson’s pathological pyramidal signs in hands, no signs in feet, hypertrophy of gastrocnemius muscles and myokymia. The patient did not have other alterations, other than indistinct polyneuritic sensory disorders in hands and feet. Illustrations of the needle myography is given below.

Figure 7 (a,b). Fibrillation and fasciculation potentials resembling neuromyotonic fasciculations

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Figure 8. Neuromyotonic potential in the upper line, neural potentials with amplitude increase, duration reduction, normal number of phases and demyelinating MUAPs.

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It is evident that the patient has an ongoing denervation-reinnervation process with Neuromyotonic potentials that require confirmation of Isaaks’ syndrome by determination of potassium channel antibodies, which is not available in Russia (16). Administered medications include azathioprine 25 mg, in the morning, after meal, supported by gastroprotectors and dicynone; eglonil 200 mg in the morning, anafranil SR 75 mg at night, seroquel 200 mg at night, one hour before meal, and depakine 500 mg in the morning and in the evening due to severe anxiety disorder – during the visit that patient asked whether it could be ALS and demonstrated primary delusion elements and anxiety (НАМ-В 33 scores). TMS has not be conducted, the patient has not come next time yet.

Example 6. ALS phobia and multiple myositis associated with the Epstein–Barr virus (the patient came for examination from Great Britain).


Patient M.R.P., 46 years old, since February 2015 she has notices catarrhal disorders with with low grade fever, then pain in joints, the posterolateral thigh, pain and swelling of muscles of arms and legs, weight loss by 2 kg, trembling chin, shaking knees and sleep disorders. Moderate increase in creatine phosphokinase to 192 U was observed, with the norm of 171 U. Examination was carried out and ultrasound revealed showed signs of tenosynovitis in the left hip abductor muscle, the pelvis and thigh X-ray revealed early signs of sacroiliac joint arthrosis, coxarthrosis, reconstruction of the bone marrow.. Chlamydia, gonorrhea, syphilis, hepatitis, HIV were not detected. Blood tests showed a decrease of ferritin, vitamin D; the CBC is not show significantly pathology, as well as biochemical analysis. In the neurological status there are no celebral, meningeal, cognitive, oculomotor and other violations of cranial innervation, except for left-sided tongue deviation. Slight head deviation with the weakness of sternocleidomastoid muscle on the right assessed up to 4.5 points. Left-sided hemiparesis in the biceps up to 4.5 points, as well as in the iliopsoas muscle, paresis of the anterior thigh muscle groups on the left up to 4 points, as well as in the ulnar group of muscles of the left hand, the left forearm hypotrophy. Tendon reflexes in arms are reduced, knee ones are of moderate vivacity, the left Achillis reflex is clonic. There are disseminated pain sensitivity disorders – hypoesthesia on the front of the left thigh, hypalgesia in the biceps on the both sides, pelvic area hypersensitivity, reduced vibration sensitivity on the left leg and foot. Diffuse red dermographism. Pelvic functions. Coordination is normal. The patient has many hypochondriacal complaints, reports on obsessive thoughts about ALS.

The needle electromyography revealed 1 positive sharp wave and 2 fibrillation potentials in the left rectus muscle of thigh. The average duration is reduced by 8.7%. The average amplitude is normal (820 μV), the maximum amplitude is increased to 2059 μV. 60% polyphasic potentials. The recruitment pattern is reduced, 17 MUAPs are recruited, there is decompensation of the primary muscle disease – myositis.

In the left biceps there is polymorphic SA manifested by multiple fibrillation potentials, positive sharp waves, the average duration is 36% below the norm, the average and maximum amplitudes are normal, multiple myopathic, myositic and reinnervation MUs. Polyphasy is increased to 80%. The recruitment pattern is saturated. Suspected myositis. The same symptoms are in the left shoulder.

Serological assays, the CBC and immunogram show signs of antibodies to the nuclear component of the Epstein-Barr virus and capsid protein, lymphocytosis, neutropenia, mild deficiency of CD3/CD8 lymphocytes. Blood biochemistry: mild hypercholesterolemia 6.2 mmol/L (the upper limit), bilirubin, glucose, triglycerides, LDL and HDL, urea, ALT, AST, total protein, CRP, calcium and potassium, lactate, parathormone, pyruvate, glucose, zinc, antibodies to Treponema pallidum in the CSF are normal, antibodies to the Epstein-Barr virus and herpesvirus 6 in the CSF are not revealed. The muscle ultrasound reveals tenosynovitis in the left thigh adductor muscle. The ultrasound of peripheral nerves is normal, stimulation of femoral, axillary, musculo-cutaneous, median, ulnar nerves is normal, except for a slight decrease in motor NCV on the ulnar nerve at the forearm. The repeated needle EMG with polymorphic spontaneous activity in muscles is presented, the histogram is denervative, but possibly the analysis does not take into account myopathic and myositic units.

Diagnosis – Effects of viral encephalitis. Viral acute multiple myositis, demyelinating mononeuropathy of the left ulnar nerve. MRI of the cervical, thoracic and lumbar spine does not reveal any significant pathology. In the brain are contrast-resistant hyperintense lesions characteristic to the effects of encephalitis, rather than for vascular disease.

Figure 9. Motor unit potentials in the biceps. Myositic units are circled in red, myopathic units are ticked, neural units are marked with “plus”. 

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The patient was administered prednisolone, i.v., for 5 days, drop infusion of high doses of dibazol, neoton, carnitine, oral administration of creatine, carnitine, lecithin, psychotropic drugs – quetiapine, depakine chrono, hopantenic acid and hydroxyzine (17).

Example 7. ALS phobia and acute lumbar myelopathy.


The patient G.A.A., male, 65 year old, was referred to electromyography of lower limbs by a surgeon. The lumbar spine MRI showed multifactor polyfactorial stenosis of the lumbar spine with L1-S1 disc herniation up to 6-9 mm and compression of neural structures. In the neurological status there is lower flaccid paraparesis up to 3-3.5 points, substantially proximal, twitching muscles of thighs, lower legs, vivacity of reflexes, foot pathological pyramidal signs, paradoxical ischuria, sensory disorders of the feet, and in the thighs and lower legs in the vertical direction. The patient also showed anxiety disorder. Before visiting the clinic he knew that we addressed ALS and began to fear this desease.

Figure 10. Giant "malignant" myokymia and fibrillation potentials in the gastrocnemius muscle.

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Figure 11. Demyelinating fasciculation potentials in the rrectus muscle of thigh. 

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Figure 12. Classic fasciculation and fibrillation potentials in the gastrocnemius muscle.

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Figure 13. Giant "malignant" myokymia and fibrillation in the rectus muscle of thigh.

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Figure 14. Giant "malignant" myokymia and fasciculations in the tibialis anterior muscle.

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Figure 15. Giant "malignant" myokymia and fibrillation in the rectus muscle of thigh.

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Figure 16. Neuronal units are ticked in red, primary denervation ones are underlined.

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The needle myography revealed radicular involvement in the forearm and deltoid muscle manifested by increase of the average and maximum MUAP amplitude without increase of polyphasy and spontaneous activity. The patient was addressed by a psychotherapeutist .

Then the patient underwent emergency pulse therapy by intravenous drop administration of solumedrol (according to the international standard) and was hospitalized to the neurosurgery department of the Eramishantsev Moscow City Hospital with the diagnosis “acute lumbar myelopathy with polyfactorial stenosis of the lumbar spine“ (18). Notably that the patient had not only fasciculations, but also myokymias of evidently “malignant” nature, which confirmed the spine irritation. However, benign myokymias in patients with ALS phobia without spontaneous activity have almost the same presentation in EMG.

Example 8. ALS phobia and hysteria.


We have described two cases of hysteria with symptoms of ALS phobia. Patient E.A.B., 32 years old, suffers from this disease for 4 years. The patient’s son has epilepsy, her husband left her. The patient regularly undergoes needle and stimulation myography, transcranial magnetic stimulation several times a year. She takes photos of her presumably affected limbs, but she fails to measure the diameters (Figure 15). She refuses to take psychotropic drugs.

Figure 17. Photos of physiological curves of the patient’s hand and feet made by the patient and delusively interpreted as atrophies.

fig19.jpg
Another patient, aged 32, sick for 5 years, regularly undergoes needle and stimulation myography, despite the fact that any nerve or muscle pathology is constantly refuted, diagnosing only relaxation disorder at the needle examination, the pattern of which looks like rhythmic rows of low potential amplitudes, which suggests that the activity is not spontaneous. The patient came for examination when she was ill, with a noninvasive ventilation device used by her husband to relieve “respiratory disorders” (panic attacks with hyperventilation). The examination showed that the patient aggravated paresis, but freely moved and used her hands. She flatly refused to conduct any gene investigation for schizotypal disorders or take psychotropic drugs.

Example 9. Celiac disease with secondary systemic carnitine deficiency and acute polyneuromyopathy


A patient, age 26, suffering from celiac disease since adolescence, visited the clinic complaining of anxiety and obsessive thoughts of ALS due to sensations of generalized muscle twitching, restless movement of feet before going to bed. During the examination no cerebral, meningeal or cognitive disorders were revealed. HAM-D score is 32 points. Cranial innervation without pathology. Right-sided hemiparesis assessed up to 3.5-4 points, predominantly in proximal muscles is revealed. The patient has hypotrophy of right limbs in proximal segments of 1.5-2 cm (the patient is right-handed), the absence of tendon reflexes, hypersensitivity of hands and feet; coordination and pelvic functions are not affected.

Complete blood count, blood biochemistry and serological tests for viral infections are in norm. Concentration of coenzyme Q10 is 0.81 mg/l (the norm is 0.4-1.6), creatine phosphokinase – 36 U/l (the norm is up to 167), transferrin – 2.07 (the norm is 2-3,5). Iron – 45.68 (normal 45,3-77,1), total carnitine – 32.8 (the norm is 35-55 μmol/L), free carnitine – 9 (the norm is 15-50,5 μmol/l). Thus, secondary systemic carnitine deficiency was revealed, which has not been described in the international literature in the context of neuropathy and in particular, myopathy (19).

The needle myography of anterior tibial muscles, rectus muscles of thigh, deltoids and common extensors of the hands on the right and on the left revealed polymorphic vigorous spontaneous activity, predominantly in the right hand. It was also characterized by giant myokymias against spontaneous activities – “malignant” myokymias the same as in the patient with lumbar myelopathy from previous case. And pseudomyotonic potentials in the most affected muscles. However, spontaneous activity was not revealed in the right leg at all. Potentials shown in Figure 18 are predominantly myophatic and neural MUAPs. Average durations are reduced by 9-37% (in the left and right anterior tibial muscles the duration is reduced by 25-37%, SA is manifested by 1 pseudomyotonic potential or not revealed), in arm muscles the duration is reduced by 9-25%. The more spontaneous activity was revealed, the less the reduction percent was, which, obviously, reflected reinnervation processes in arms, while in legs “static” myopathy was observed.

Figure 18. Myopathic MUAPs are underlined in red, neural ones are ticked.

fig20.jpg

The patient was administered carniton 1 g, 3 times a day, for long-term use, 10% carnitine chloride 10 ml per 200 ml of saline solution No. 15, i.v., by drop administration, lipoic acid 24 ml per 200 ml of saline solution No. 15, i.v., by drop administration, lecithin 6 g per day for 2 months, psychotropic drugs (quetiapine 100 mg, at night, one hour before meal, depakine chrono 500 mg, 1 tablet twice a day, hydroxyzine 25 mg in the afternoon and in the evening, pantogam 250 mg three times a day, Lactis-5 and gluten-free diet.

It should be noted that we observe a patient with ALS with slow progression, who was diagnosed dissociative disorder three years ago. In our view and in the opinion of foreign authors, additional macroelectromyography would be an adequate measure to prevent pre-clinic ALS in this case, as well as in case all ALS phobias (5,6,18-19).

Follow-up observation and the possibility of treatment, both psychotropic and neurotropic, would be available for 30 (25%) persons. The patients, who came for dynamic monitoring 2 to 4 times and received atypical antipsychotics (quetiapine, i.e. seroquel 25-10 mg or seroquel prolong 20 mg), tymoleptics, valproic acid. i.e. depakine chrono 500 mg 1/2 tablets twice a day), sometimes anafranil 25 mg at night, eglonil 50 mg in the morning and in the afternoon (in case of concurrent gastrointestinal pathology) together with basic seroquel or depakine chrono therapy. Patients with alcohol addiction were advised psychotherapy and prescribed metronidazolе 500 mg twice a day, fluanxol 2-4 mg per day and Akineton2 mg per day, which also resulted in positive dynamic. In some cases selective serotonin reuptake inhibitors were prescribed as antidepressants and Z-hypnotics. As a result, the average treatment period of the phobia was 11 months and the HAM-D score decreased from 19.7±6.1 to 10.3±7.9, which was statistically significant (p = 0.0001). Neurotrophic therapy included blockade with hormonal and analgesic drugs for tunnel syndromes and vertebral radicular syndromes, therapeutic massage, manual therapy, planterotherapy (plantar massage), physiotherapy, chondroprotective and gastroprotective non-steroid anti-inflammatory drug (tenoxicam), myotropic and neurotrophic metabolic drugs (carnitine, creatine, B vitamins, lipoic acid, lecithin), vascular, nootropic, antihypertensives or other drugs, as required.

Discussion


Complex clinical and electromyographic study of ALS phobia with elements of molecular genetic testing showed that EMG did not reveal any pathology in approximately 65% of patients, or signs of chronic radicular involvement without spontaneous activity in the muscles, which in view of variability of such parameter as MUAP amplitude, psychogenic relaxation disorders, a lack of correlation with increase of the MUAP amplitude with spine neurovisualization data can be considered as primary phobia with benign myokymias taken by patients for fasciculations. Of course, in some cases we proved mental diseases and disorders of schizotypal nature in the group of patients (11.6%), however, genetic tests were needed for the remaining 53.4% of patients, but they refused. Particularly informative are DAT-1 investigations, while DRD4 investigations were useless in all cases. The investigation of such genes is required for control patients – healthy people or people diagnosed with mental disorders without ALS. It is noteworthy that in patients with proved mental disorders – clinic or genetic ones – neurological disorders may be revealed by electromyography (Example 2) or not (Example 1). In other 23,4% cases various nerve and muscle diseases, syndromes of peripheral neuromotor apparatus disorders were observed. It has been shown that in cooperative patients the treatment of phobic symptoms with the mentioned groups of medications result in phobia regression approximately within 11 months. Some patients may need macroelectromyography, which can reliably refute the diagnosis of pre-clinic ALS and should be prescribed for diagnostic and psychotherapeutic purposes (5,6,18-19). Adverse impact of antidepressants in patients with anxiety disorders was noted in respect of phobic symptoms – it is obvious that this group of medications should be prescribed as monotherapy in no way, which, unfortunately, is the most common mistake of neurologists who had consulted out patients before they came to our clinic (21). It should be noted that in general the level of cooperation in patients with ALS phobia in most cases is very low (25% of repeated observations with treatment).

Significantly that for the recent three years the term “ALD phobia” has not become common for the Russian neurology and the terms “dissociative motor disorder”, “somatoform disorder”, etc. are more commonly used for the description of this syndrome (2). We plan to address the International Classification of Diseases regulators to include ALD phobia in the list of specific phobic disorders of ICD-10.

It is interesting that among our patients we observed those with thyroid disease, who, according to the literature, can suffer from shyzotypal disorders of the dysmetabolic origin – thus, in the study of G.P. Ivanova and A.L. Gorobets 17-18% of persons with alexithymia and Hashimoto's thyroiditis suffered from schizotypal personality disorders, or schizoidia (22). The identification of so called “malignant” myokymias in the patient with acute lumbar myelopathy and in the other patient with celiac disease and acute polyneuromyelopathy with secondary carnitine deficiency was also quite interesting. The data suggest that myokymias should not be abidingly defined as benign potential.

The identification of so called “malignant” myokymias in the patient with acute lumbar myelopathy and in the other patient with celiac disease and acute polyneuromyelopathy with secondary carnitine deficiency was also quite interesting. The data suggest that myokymias should not be abidingly defined as benign potential.

It is noteworthy that the level of cooperation among neuromuscular pathology consultants is quite low in Russia, as well as moral and ethic principles of some of them, their use of absolvent classification methods for electromyographic disorders (we mean classification of stages of the denervation-reinnervation process by B.M. Gekht and L.F. Kasatkina), which are not efficient for some combined forms of neuromuscular pathologies and may result in diagnostic mistakes (5,6). It is obvious that the key to a successful myographic diagnosis of neuromuscular diseases and syndromes of neuromotor disorders in this study is the use of extended MUAP analysis (20-30 units) and a wide use of neurovisualization methods and TMS, methods of laboratory, biochemical and serological diagnosis. We believe that a modern myography specialist should assess and interpret individual MUAP rather than reduce the analysis to the mere calculation of deviations in the duration, amplitude and polyphasy from the norm. We should also notice that dealing with patients we learnt about violations of ethics and deontology principles by neuromuscular consultants – patients with ALS phobia were often diagnosed ALS or were not diagnosed at all and they were advised to consult a psychiatrist, which could lead to a lack of diagnosis of the neurological pathology in 23.4% of cases, moreover, such consultants spoke disrespectfully about their colleagues.

It is obvious that the aid provided to patients with ALS phobia should consist of a joint inspection with an experienced neurologist, neurophysiologist (an electromyography specialist) and a psychiatrist experienced in differential diagnosis of ALS and other neuromuscular diseases in order to persuade patients that they are mistaken about their interpretation of what is going on and prescribe reasonable psychotropic, neurotropic and psychotherapeutic complementary (distractive) therapies. Unfortunately, psychiatrists, who had consulted our patients before they came to us, lacked eagerness to understand the pathology, and neurologists together with electromyography specialists were largely disposed to assign the developed syndrome the psychiatry's domain, which resulted in the “interdisciplinary footballing” of patients with a potentially curable pathology. In Russia, the level of ALS diagnosis is quite low. Gross errors are often made even by doctors who show off their scientific degrees and titles, including some doctors of biological sciences, who have neither a neurologist’s diploma, nor a functional diagnostics doctor’s diploma, which is a legal precedent. It is clear that hyper- or hypodiagnosis of ALS by such specialists recommending to carry out electromyography in dynamics every 3 months will lead to increased anxiety disorders in patients, their continued incapacity to work and premature disability. However, according to international data, about 40% of ALS patients are not satisfied with how the diagnosis is presented abroad, as well as with the work of neuromuscular consultants (23).

References


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