Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies

A novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.     

Acute-onset painful upper limb multifocal demyelinating motor neuropathy

We report three patients who presented with acute onset of shoulder and upper arm pain followed within a few days by predominantly distal upper limb weakness. Nerve conduction studies showed severe and unequivocal focal motor conduction block in the forearm and/or upper arm along with slowing of motor conduction and prolonged F wave responses. Only very mild changes in sensory nerve conduction were found. One patient made partial clinical improvement after 17 months, and there was a significant improvement in the degree of motor conduction block and the motor conduction velocities. A second patient remained unchanged after 5 months. Idiopathic brachial neuritis (IBN) typically presents acutely with brachialgia and acute or subacute non-progressive weakness. Multifocal motor conduction block in nerves in the arm or forearm has not been described in patients with IBN. Multifocal motor conduction block restricted to the upper limbs has been described in focal chronic inflammatory demyelinating polyneuropathy (CIDP) and in multifocal motor neuropathy with multifocal motor conduction block (MMNCB). However, both these conditions have hitherto usually been described as largely painless chronic progressive disorders with a subacute onset. Our patients, with features overlapping MMNCB/CIDP and IBN, represent an as yet unreported clinical variant. Received: 9 February 2000 / Received in revised form: 18 May 2000 / Accepted: 28 June 2000     

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically. The facial nerve motor neurography was abnormal in 17 of 19 HMSN I patients and in both HMSN III patients, revealing moderate to marked conduction slowing in both the extracranial and intracranial nerve segments, along with variable reductions of compound muscle action potential (CMAP) amplitudes. The facial nerve conduction slowing paralleled that of limb nerves, but was not associated with clinical dysfunction of facial muscles, because none of the HMSN I patients had facial palsy. Conduction slowing was most severe in the HMSN III patients, but only slight facial weakness was present. In GBS, conduction slowing was less marked, but facial weakness exceeded that in HMSN patients in all cases. We conclude that involvement of the facial nerve is common in HMSN I and HMSN III. It affects the intra- and extracranial part of the facial nerve and is mostly subclinical.     

Multifocal motor neuropathy presenting as chronic progressive proximal leg weakness

We report on a 47-year-old man with a 12-year history of progressive and ultimately severe proximal weakness of his right lower limb. Motor conduction block at the unaffected tibial nerve and positive IgM antibodies against GM1 gangliosides lead us to suggest a diagnosis of oligosymptomatic multifocal motor neuropathy. He rapidly responded to intravenous immunoglobulins, with complete remission lasting 4 weeks, and had a repeated treatment response to intravenous immunoglobulins during subsequent exacerbations. The proximal involvement may represent another unusual clinical manifestation of multifocal motor neuropathy.     

Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy

OBJECTIVE: We present the electrophysiologic data at baseline of 37 patients who were included in our prospective study on sporadic adult-onset progressive muscular atrophy (PMA). The aim was to correlate electrophysiological signs of lower motor neuron (LMN) loss with clinical signs of LMN loss, and to determine the prognostic value of the distribution of electrophysiological abnormalities in patients who presented clinically with only lower motor neuron signs. METHODS: Thirty-seven patients, who met our inclusion criteria for a prospective study on sporadic adult-onset PMA, underwent extensive standardized electrophysiological examination at baseline, consisting of concentric needle EMG in three regions (cervical, thoracic and lumbosacral) and standardized nerve conduction studies. RESULTS: Denervation on needle EMG was found in 88 % of clinically affected and in 40 % of clinically unaffected limb regions. All patients with a segmental or distal phenotype at baseline who developed generalized weakness had denervation in the thoracic region. Motor nerve conduction abnormalities were found in a substantial number of nerves and included reduced CMAP amplitude, increased distal motor latency, decreased motor conduction velocity, and F-wave abnormalities. Signs of demyelination and sensory nerve conduction abnormalities were rare. CONCLUSIONS: Our electrophysiological data in patients recently diagnosed with sporadic progressive muscular atrophy are consistent with widespread LMN loss. Progression in patients with a segmental or distal onset of PMA may be likely if denervation is found in clinically unaffected regions, including the thoracic region.     

Peripheral and central conduction studies in neurolathyrism.

To study the involvement of motor and sensory pathways in neurolathyrism, 19 patients with lathyrism from Unnao, India, where lathyrism is endemic, were studied. The mean age of the patients at the time of the onset of illness was 35.8 (range 18-70) years. The mean duration of illness was 15.6 (range 2-30) years. The clinical picture comprised walking difficulty due to stiffness and mild weakness in all 19 patients, cramps in the legs in five, frequency or urgency of micturition in five, and flexor spasms in three. There was pronounced leg spasticity with a mean Ashworth score of 4.1 (range 2.9-5). Central motor conduction to the tibialis anterior muscle (CMCT-TA) was slow in 14 of the 17 patients (21 sides). Slowing of peripheral motor nerve conduction, although less pronounced, was significant in the upper limb in four and the lower limb in seven sides. The tibial somatosensory evoked potentials were normal and peroneal nerve conduction was marginally impaired. Values for CMCT-TA correlated with the degree of spasticity (p < 0.02) whereas weakness, crossed adductor reflexes, and clonus did not. The wide variability of CMCT-TA in lathyrism may be due to involvement of different types of fibres. Large diameter fibre involvement may cause pronounced slowing. Small diameter fibre involvement could produce appreciable spasticity and mild weakness but a lesser degree of slowing or even normal conduction.     

A family of hereditary motor and sensory neuropathy with spastic paraplegia (HMSN type V) presenting with phenotypic uniformity including onset in early childhood]

The proband was a 38 year old mother, who had begun to walk abnormally at one year old. She developed weakness and wasting in the intrinsic hand muscles in the third decades. On neurological examinations, she showed weakness with atrophy in the distal muscles of the upper and lower limbs, mild impairment of deep sensation in the feet, and severe spastic gait with scissoring. Deep tendon reflexes were hypoactive in the arms and at the ankles, and brisk at the knees. Babinski sign was present bilaterally. Nerve conduction studies revealed mild slowing of conduction velocities and reduction of muscle and sensory action potential amplitudes. Sural nerve biopsy showed a prominent decrease in myelinated fiber density, especially in the large fibers. Neither demyelination nor typical onion-bulb was found. Results of gene analysis of PMP-22 was negative. Her two daughters, 14- and 11-year-old, respectively, also presented with gait disturbance from the beginning of walking at one year old and had almost the same clinical manifestations as their mother, indicating autosomal dominant inheritance. This family of the hereditary motor and sensory neuropathy with spastic paraplegia (HMSN type V) was distinctive in having phenotypic uniformity including onset in early childhood.     

A syndrome of asymmetric limb weakness with motor conduction block

We describe 3 patients with asymmetric limb weakness, fasciculations (2 patients), relatively preserved reflexes, normal cranial nerves, and few or no sensory abnormalities. The symptoms had been progressive over 1 to 15 years. Detailed motor nerve conduction studies showed conduction block and slowing localized to sharply circumscribed areas 30 to 100 mm long in several nerves in each patient. By contrast, the sensory conduction studies over the same nerve segments were normal, indicating very selective involvement of motor fibers. Sural nerve biopsies showed minor changes that varied among the patients. One patient had high levels of anti-GM1 antibodies, 1 had mildly elevated levels, and 1 had high levels of only asialo-GM1 antibodies. Treatment with immune suppressive therapy has produced minimal improvement in 1 patient.     

Limb motor nerve dysfunction in Miller Fisher syndrome

Typical Miller Fisher syndrome (MFS) lacks limb muscle weakness, but some patients may unpredictably progress to severe Guillain‐Barré syndrome. The compound muscle action potential (CMAP) scan is a recently developed non‐invasive, painless, and reproducible method for detecting early changes in motor nerve excitability. This technique was used to monitor subclinical limb motor nerve dysfunction during disease course in typical MFS. Three Miller Fisher patients with preserved limb muscle strength and normal routine nerve conduction studies were included. Frequent serial CMAP scanning of the median nerve was performed during acute phase and follow‐up and was related to clinical course and outcome. All patients showed an abnormal increase in the range of stimulus intensities at the day of hospital admission, indicating reduced motor nerve excitability already at the earliest stage of disease. Median nerve dysfunction progressed in parallel or even before clinical deterioration, and improved with clinical recovery. Our study shows that typical MFS is a more general neuropathy, affecting peripheral motor nerves even in patients with preserved limb strength and conduction velocity. CMAP scanning is a sensitive technique for early detection of subclinical motor nerve dysfunction and for monitoring disease activity in immune‐mediated neuropathies.     

PHENOTYPE OF PMP22 TRANSGENIC SCHWANN CELLS IN CULTURE

We describe the case of an Italian 51-year-old woman who developed a particular descending paralysis after severe pharyngeal infection. When she was taking a holiday in Madagascar she suffered a severe pharyngeal infection with pseudomembranes, neck oedema that lasted almost one month despite antibiotics treatment. One month after the infection, she developed a left lower cranial paralysis causing palatal and pharyngeal weakness, blurring of vision as a result of paralysis of accommodation. A severe descending paralysis followed consisting of weakness of limbs and paresthesia of extremities. EMG showed prolonged distal motor latencies, absence of F wave in the median nerve, and normal value of motor and sensory nerve conduction velocities.
Since the primary pathologic change is segmental demyelination, slowing of sensory and motor conduction velocity is a common electrophysiological finding. However, decreased conduction velocity and increased distal motor latency may not be present two weeks after the onset of neurological symptoms, and maximal electrophysiological abnormalities may be found after clinical recovery has began.
We report this particular clinical picture to remind that adults vaccinated in childhood do not continue to have sufficient immunity to protect against diphtheria so diphtheritic neuropathy must be kept in mind because the clinical signs are similar to those seen in the Guillain Barré syndrome and the distinction between the two is sometimes difficult.     

An autopsy case with lower motor neuron disease showing a transient-appearance of anti-GM1 antibody and an improvement of conduction block after gamma-globulin administration]

We report a 63-year-old man who died of respiratory failure. He was well until 1992 (57 years of his age), when he had an onset of progressive weakness of the bilateral upper limbs. He showed no improvement with TRH administration in other hospital. On January 12, 1994, he admitted to our department because of the progressive muscle weakness. Neurologic examination revealed a muscular atrophy associated with severe weakness and hyporeflexia in both upper limbs, and fasciculation were seen in his tongue. Electrophysiological studies revealed mild conduction block in the left medial nerve, and F-waves were not evoked in the left ulnar nerve and bilateral median nerves. After an administration of 25 g/day of human gamma-immunoglobulin for 5 days, conduction block as well as F-wave abnormalities in the left median and left ulnar nerve were improved, yet no improvement of muscle weakness was seen. The anti-GM1 IgG titer was transiently elevated in the patient's serum after gamma-immunoglobulin therapy. On September 8, 1994, subtotal gastrectomy was performed because of the early stage gastric cancer. Histological examination showed poorly differentiated adenocarcinoma (signet-ring cell carcinoma). His muscle weakness had been gradually extended to the lower limbs and he couldn't walk himself on January, 1998. On March, 1998, he developed tetraplegia, mild dysphagia, dysuria and the respiratory disturbance. On April 12, 1998, he admitted to our department for the second time. Neurologic examination revealed a muscular atrophy and fasciculation associated with severe weakness in all of his limbs, tongue and musclus masseter. Neither deep tendon reflex nor pathologic reflex was evoked in his upper and lower extremities. His ocular movements and sensations were well preserved. He died of respiratory failure on May 1, 1998. The patient was presented in a neurological CPC. Neurological and laboratory findings suggested a spinal progressive muscular atrophy (SPMA). However, there were several unusual points as a typical SPMA in this case, that is, an improvement of the electrophysiological abnormalities by gamma-globulin treatment, as well as transient elevation of anti-GM1 antibody. The clinical neurologists have arrived at the conclusion that the patient had lower motor neuron syndrome associated with anti-ganglioside antibody and cause of death was ascribed to the respiratory failure. We discussed whether this case was SPMA or multifocal motor neuropathy. Postmortem examination revealed numerous diverticulums in the ascending colon and lymphothyroiditis. No recurrent carcinoma was detected. Neuropathologically, both severe atrophy of the anterior spinal roots, and severe gliosis and neuronal loss in the anterior horn of the spinal cord were observed. Onuf nuclei were not affected. Neurogenic muscular atrophy was detected in the tongue, diaphragm, and limb muscles. Motor neurons of the brainstem were relatively preserved, but skein-like inclusions as detected by anti-ubiquitin antibody, were present in the facial and hypoglossal nuclei. Neither motor cortex nor cortico-spinal tracts were affected. Demyelination, remyelination or cellular infiltrations were not apparent in the right median nerve and sciatic nerves. The neuropathologic features were compatible with SPMA.     

New trends in neuropathy practice: clinical approach to CIDP]

Our recent study showed that the overall prevalence of CIDP was estimated as 2.2 per 100,000 population in Aomori Prefecture, in Northan Honshu of Japan. In our series of more than 80 cases with CIDP, a chronic acquired inflammatory demyelinating polyneuropathy, nearly 30% showed clear laterality of weakness, and electrophysiologic laterality or multifocality was apparent in almost all cases. Nearly 90% of patients were able to walk without walking aids or other assistance. Sixty% showed distal dominant muscular weakness. In 12 patients with age of onset under 15, pes cavus deformity was seen in 5. Two thirds complained numbness in the extremities during progressive phase. Four cases initially showed severe sensory ataxia associated with motor conduction block. It should be, thus, reminded that clinical spectrum of CIDP is enormously wide: chronic acquired demyelinating multiple mononeuropathy showing asymmetric involvement (Lewis-Summer syndrome) should be put on one side of the clinical presentation of CIDP. Multifocal motor neuropathy (MMN) is, on the other hand, an unique syndrome mimicking amyotrophic lateral sclerosis (ALS). There may be, however, true association syndrome of CIDP and ALS presenting both peripheral nerve demyelination and pyramidal sign with progressive bulbar involvement. Recently, several atypical varieties of CIDP showing only one-limb involvement, upper limb weakness rather than lower limb power loss, or proximal weakness, etc ... have been reported in the literature. To realize such clinical variations of chronic acquired demyelinating neuropathy is important for early diagnosis and commencement of treatment of CIDP. Clinical guideline for suspicion of CIDP could be useful for general physicians and neurologists unfamiliar to peripheral neuropathies.     

Proximal axonal changes after peripheral nerve injury in man

Peripheral nerve injury leads to changes in the proximal axon. Traumatic nerve injuries in humans were investigated to characterize such electrophysiological changes. Mixed nerve conduction studies (MNCS) and motor conduction studies (MCS) were performed proximal to the injury. Control values were obtained from the uninjured limb. Median (n = 24) and ulnar (n = 35) nerve injuries were studied. The injured nerves had significant mixed nerve action potential (MNAP) amplitude reductions (median: P < 0.0001; ulnar: P < 0.0001). The majority of the MNAP amplitude reductions were severe and early. There was slowing in the mixed nerve conduction velocity (MNCV) (median: P = 0.09; ulnar: P = 0.04) and motor conduction velocity (MCV) (median: P = 0.046; ulnar: P = 0.005). Axonal loss appears to play a significant role in producing the MNCS changes observed, and its early occurrence is noteworthy. Proximal MCV reduction could be secondary to the effects of injury as well as collateral sprouting of uninjured axons. Proximal axonal changes may have an impact on recovery.     

Multifocal motor neuropathy presenting with respiratory failure

Multifocal motor neuropathy is a disorder characterized by slowly progressive asymmetrical limb weakness and multiple motor conduction blocks. We report a 56-year-old woman with this disorder who presented unusually with respiratory failure and who initially had absent responses to phrenic nerve stimulation bilaterally. The mechanism of the patient's respiratory failure may have been chronic conduction blocks in the phrenic nerves leading to diaphragmatic weakness.     

Conduction in the motor neurons of the peripheral nerves in hemiplegia of cerebral origin

A study of motor nerve conduction velocities in median, ulnar, peroneal and tibial nerves bilaterally in 50 hemiplegic patients revealed a statistically significant slowing in the affected limbs compared with the unaffected side. The decrease of nerve conduction velocity was not related to any of the following factors: duration of stroke, degree of paralysis, degree of spasticity, side of paralysis, age of patients, and sex ef patients. The results can indicate that lower motor neurons are indeed affected by upper motor neuron lesions. The slowing of the nerve conduction velocity of motor peripheral nerves is probably due to the loss of trophic influence from higher centres or its decline. The author suggests that this phenomenon leads to a selective deterioration of thick nerve fibres while only thinner ones continue conducting impulses.     

Dystrophia myotonica. Peripheral nerve involvement and pathogenetic implications.

A comparative electrophysioloical study of patients with dystrophia myotonica and control subjects is presented. The study includes estimation of the number of motor axons innervating the extensor digitorum brevis muscle and measurements of the conduction of M- and F-waves along the deep peroneal nerve. There is unequivocal electrophysiological evidence of nerve involvement in the disease. This was indicated by (a) prolongation of the terminal latencies and slowing of the motor conduction of the deep peroneal nerve (P less than 0.001), (b) delayed conduction of the F-wave along the proximal segments of the nerves (P less than 0.02-0.01), (c) reduced number of motor axons innervating the extensor digitorum brevis muscle (P less than 0.001), (d) high amplitude motor unit potentials and discrete EMG activity on the maximal volitional contraction of minimally affected muscles in one patient. However, if the muscle changes were secondary to the nerve involvement occurring in the disease, one would expect that the electrophysiological findings of neuropathy would become more prominent in patients with severe muscle wasting and weakness. Our results showed that in some patients with marked muscle atrophy and weakness there was no evidence of nerve involvement while in other patients with slight to moderate degree of muscle weakness the electrophysiological studies indicated peripheral neuropathy. Therefore, it appears that both the nerves and the muscles are independently affected by the pleiotropic action of the responsible gene and the evidence does not suggest that the muscle atrophy of patients with dystrophia myotonica is entirely neural.     

Electrodiagnostic abnormalities in 113 consecutive patients with Guillain-Barré syndrome

We performed electrodiagnostic tests on 113 consecutive patients with acute Guillain-Barré syndrome (103 within 3 weeks of onset). The most common motor conduction abnormalities were proximal conduction block alone (27%), proximal block associated with a distal lesion (27%), and generalized slowing (22%). Other combinations of abnormalities each occurred in fewer than 10% of patients. Thirty-seven percent of patients initially had normal sensory nerve conduction study results, most often in association with proximal conduction block. The characteristic early electrodiagnostic changes in Guillain-Barré syndrome were often present when cerebrospinal fluid protein concentration was still normal. Extensive early fibrillations occurred in 10 patients, 6 of whom recovered well. Patients with early generalized slowing of motor nerve conduction velocity, combined abnormalities, or low muscle action potential amplitudes in ulnar, median, and peroneal nerves generally, but not always, had poorer outcomes than patients with conduction block in one nerve segment. There was no consistent relationship between results of electrophysiologic studies and overall clinical grade or limb power, except that none of the patients with an isolated proximal block had virtual or complete paralysis in the same limb.     

Peroneal muscular atrophy with pyramidal features.

Twenty-five cases of peroneal muscular atrophy with pyramidal features from 15 families are described. This disorder has been referred to as hereditary motor and sensory neuropathy (HMSN) type V by Dyck. Onset was usually in the first two decades of life with difficulty in walking. The clinical syndrome superficially resembled that of HMSN types I and II with distal wasting and weakness involving the legs more than the arms. The tendon reflexes in the upper limbs and at the knee tended to be normal or increased but the ankle jerks were often absent. The plantar responses were extensor in 22 patients, absent in two and flexor in one. Increased tone and weakness in the proximal lower limb muscles were found in about 30% of cases. Mean motor nerve conduction velocity was lower than in normal controls and sensory nerve action potentials were reduced in amplitude or absent in two thirds of the patients studied. Inheritance was autosomal dominant in the majority of families. The disorder was slowly progressive but did not lead to severe disability.     

Motor neuropathy associated with a facilitating myasthenic syndrome

We report a patient with progressive muscle weakness, areflexia, and no sensory loss. Electromyography revealed normal sensory nerve conductions, mild slowing of motor nerve conduction velocities, low amplitude compound muscle action potentials, a neuromuscular transmission defect characterized by prominent facilitation, and diffuse fibrillation potentials. Muscle biopsies showed acute denervation atrophy, and at autopsy, there was anterior horn cell loss and gliosis in the spinal cord. The findings suggest the coexistence of a motor neuropathy and a facilitating myasthenic syndrome.     

Compression of the ulnar nerve at the elbow by an intraneural ganglion.

A rare cause of ulnar nerve compression at the elbow is presented in this report. A 42 year old right-handed mechanic developed subacute, progressive numbness, tingling and weakness in his right hand. Electrophysiologic studies demonstrated a severe conduction block affecting the ulnar nerve in the retrotrochlear groove but without any sign of major axonal loss. His hand functions were carefully studied prior to surgery. While fine motor tasks were not affected, the hand strength was markedly diminished. At surgery, a 1-cm diameter intraneural ganglion at the site of the conduction block was found and excised. The patient made a dramatic recovery within 6 weeks post-surgery. The conduction block completely resolved and the hand functions also returned to normal. This and other reported cases point to the importance of early diagnosis and intervention.