A case of acute autonomic, sensory and motor neuropathy (AASMN)--less favorable response of the autonomic dysfunctions to IVIg treatment]

We report a rare case of acute autonomic, sensory and motor neuropathy (AASMN). The patient, a 26-year-old woman, developed fever and common cold around January 20, 2001 and was admitted because of abdominal pain due to ileus on January 30. After admission, the patient complained of muscle weakness and numbness in the extremities, difficulty in seeing with the right eye, and dysuria. Neurologically, marked orthostatic hypotension, right tonic pupil, distal dominant moderate muscle weakness in extremities, areflexia in both lower limbs, glove and stocking type of paresthesia, and neurogenic atonic bladder were noted. Sensation to pin prick, light touch, temperature, and vibration were markedly impaired in upper limbs and below the level of the 5th thoracic cord. Cerebrospinal fluid examination revealed albumino-cytologic dissociation. Peripheral nerve conduction study revealed lower limb dominant axonal type impairment of sensory conduction and slight impairment of motor conduction velocity. Clinical autonomic testings revealed dysfunction of both sympathetic and parasympathetic systems. As having AASMN, she was given the intravenous high-dose immunoglobulin (IVIg) therapy twice. After IVIg, the sensory and motor symptoms improved remarkably, but pandysautonomia did not. To our knowledge, this is the first report of AASMN treated by IVIg, and the notable clinical feature in this case was the favorable motor and sensory recovery to IVIg, as opposed to poor autonomic outcome.     

Acute autonomic sensory and motor neuropathy associated with parvovirus B19 infection

We report a 9-year-old girl with acute autonomic sensory and motor neuropathy (AASM) associated with human parvovirus B19 (HPV-B19) infection. The patient presented with fever, erythema of the entire body, and abdominal pain with vomiting. The titer of HPV-B19 IgM antibody was significantly elevated. Symptoms such as muscle weakness, severe hyperesthesia, dyshidrosis, and neurogenic bladder associated with autonomic disturbance developed over several days. Intravenous immunoglobulin therapy gave no obvious improvement of her symptoms. Motor and sensory impairment improved slowly without medical treatment, but dysautonomia persisted for a long time. Sural nerve biopsy revealed axonal degeneration of small fibers, involving both myelinated and unmyelinated fibers, which is compatible with the autonomic sensory and motor neuropathy. AASM is very rare in pediatric populations, and there is no report of AASM associated with HPV-B19 infection.     

A case of spinocerebellar ataxia accompanied by severe involvement of the motor neuron system

We report a sporadic case of spinocerebellar ataxia accompanied by later but severe involvement of the motor neuron system. A 72-year-old man began to show ataxia and dysarthria at age 66 years. Neurological examinations revealed saccadic eye movement, slurred speech, truncal ataxia, pyramidal sign, and urinary disturbance. Neither history of alcoholism nor hereditary factors were found. He developed muscular atrophy of the lower and upper extremities and limb ataxia within three years. Superficial and deep sensations were diminished in both feet four years after onset. Thus, he presented with cerebellar ataxia, bulbar sign, upper and lower motor neuron symptoms, sensory disturbance, and autonomic sign after six years at age 72. The level of serum, creatine phosphokinase (CPK) was increased, and muscle biopsy showed marked neurogenic change. Magnetic resonance imaging (MRI) revealed mild cerebellar and pontine atrophy. Although the combination of spinocerebellar ataxia and motor neuron disease is very rare, the present case suggests the inter-relation of the spinocerebellar and motor neuron systems, and presents peripheral neuropathy as a subtype of multisystem atrophy.     

Dementia of frontal lobe type due to adult polyglucosan body disease

We describe a patient with adult polyglucosan body disease (APBD) who presented with a dementia of frontal lobe type (FLD), with a neurogenic bladder but no symptoms of sensory motor peripheral neuropathy. Diagnosis was made from a cerebral biopsy specimen which showed an accumulation of intra-axonal polyglucosan bodies in the central nervous system. This case differs from the usual presentation, in which gait disturbance is the main symptom and diagnosis is possible by sural nerve biopsy. Little is known about the neuropsychological pattern of APBD dementia but FLD has not previously been described. APBD is a heterogeneous clinical entity of unknown cause. This diagnosis must be considered in elderly patients with dementia.     

Peripheral neuropathy associated with chronic natural killer cell lymphocytosis

We report a patient with steroid-responsive peripheral neuropathy which developed with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with a 2-week history of progressive motor and sensory neuropathy showed a marked increase of natural killer (NK) cells in the blood, and was diagnosed as having CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve fascicles, and demyelinating changes with axonal degeneration. The infiltrating NK cells were adjacent to myelinated fibers, showing damage of Schwann cell membrane. Treatment with oral prednisolone resulted in rapid improvement of the sensory disturbance and weakness with a significant decrease of NK cells in the blood and disappearance of the conduction blocks in NCS. This is the first case of CNKL associated neuropathy in which infiltration of NK cells was demonstrated in the nerve fascicles. Our observations suggest that the infiltrating NK cells may directly damage myelin and Schwann cells, thus causing demyelination.     

Hereditary sensory and autonomic neuropathy type I in a Chinese family: British C133W mutation exists in the Chinese

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disorder of the peripheral nervous system characterized by marked progressive sensory loss, with variable autonomic and motor involvement. The HSAN I locus maps to chromosome 9q22.1–22.3 and is caused by mutations in the gene coding for serine palmitoyltransferase long chain base subunit 1 (SPTLC1). Sequencing in HSAN I families have previously identified mutations in exons 5, 6 and 13 of this gene. Here we report the clinical, electrophysiological and pathological findings of a proband in a Chinese family with HSAN I. The affected members showed almost typical clinical features. Electrophysiological findings showed an axonal, predominantly sensory, neuropathy with motor and autonomic involvement. Sural nerve biopsy showed loss of myelinated and unmyelinated fibers. SPTLC1 mutational analysis revealed the C133W mutation, a mutation common in British HSAN I families.     

Welander''s distal myopathy: clinical, neurophysiological and muscle biopsy observations in young and middle aged adults with early symptoms.

Nine young or middle aged patients with early symptoms of Welander's distal myopathy were subjected to a detailed neurological examination including quantitative sensory testing, determination of motor and sensory nerve conduction velocity (NCV), sensory nerve action potentials, electromyography (EMG) and muscle biopsy from the tibialis anterior muscle (TA). Slight weakness of the extensors of the fingers and hands was found in all nine patients, and of the dorsiflexors of the feet in seven. All patients had a distal sensory disturbance most prominent for temperature which agrees with earlier observations. EMG changes in TA and extensor digitorum communis (EDC) muscles were of myopathic type. Slight abnormalities compatible with either myopathy or early neuropathy were found in one muscle biopsy. These findings indicate that a neurogenic lesion affecting at least the peripheral sensory system is present at an early stage of Welander's distal myopathy and that the neurogenic lesion might precede the myopathic changes.     

Late‐onset hereditary sensory and autonomic neuropathy expands the phenotypic spectrum of MFN2‐related diseases

Mutations in the Mitofusin 2 (MFN2) gene have been identified in patients with autosomal dominant axonal motor and sensory neuropathy or Charcot–Marie‐Tooth 2A (CMT2A). Here we describe clinical and pathological changes in an adult patient with sporadic hereditary sensory and autonomic neuropathy (HSAN) due to an MFN2 mutation. The patient was a 53‐year‐old man who had sensory involvement and anhidrosis in all limbs without motor features. The electrophysiological assessment documented severe axonal sensory neuropathy. The sural nerve biopsy confirmed the electrophysiological findings, revealing severe loss of myelinated and unmyelinated fibers with regeneration clusters. Genetic analysis revealed the previously identified mutation c.776 G > A in MFN2. Our report expands the phenotypic spectrum of MFN2‐related diseases. Sequencing of MFN2 should be considered in all patients presenting with late‐onset HSAN.     

N-hexane neuropathy in offset printers.

In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered.     

A family of hereditary motor and sensory neuropathy with spastic paraplegia (HMSN type V)

Three siblings with hereditary motor and sensory neuropathy with spastic paraplegia (HMN V) were described. Their grandfather was suspected to have the similar symptoms. Their parents were normal and not consanguineous. The first case was a 54-year-old woman. She has suffered from difficulty in walking since the age of 10 years. Distal muscular weakness and wasting began at 20 years old. She was admitted to our hospital for investigation in 1988. Results of examination of the brain, cranial nerve, and cerebellar function were normal. The deep reflexes were hyperactive in the arm and knee, while absent at the ankle. Babinski's sign was definitely positive. Muscular weakness and wasting were noted in intrinsic hand muscles and in those below her knees. There were pes cavus and hammer toes, and the gait was spastic. Mild sensory disturbance was noted in distal limbs. The conduction velocity of motor nerve fibers of her limbs was below normal and that of sensory nerve fibers normal. Muscle biopsy of biceps brachii revealed neurogenic changes. Sural nerve biopsy showed decreased number of myelinated fibers of large diameter and formation of small oinion-bulb. The second and third cases were her brothers and proven to have the similar condition, but their onset of illness were earlier and their affections were more severe. A few cases of HMSN V with nerve biopsy findings have so far been reported and the family presented here is the first report in Japan.     

A case of malignant thymoma associated with Eaton-Lambert-type neuromuscular transmission block and sensorimotor neuropathy

The patient is a 73-year-old male. In January 1988, he noticed sensory disturbance and muscular weakness of his extremities. His thymoma was found in July 1988, and in October 1988, he was admitted to our hospital for treatment. Neurological examination showed muscular weakness, muscular atrophy, fasciculation, and distal dominant sensory disturbance of his right upper extremity and his bilateral lower extremities. The immunological examination showed an increase in serum IgG, gamma-globulin, OKT3 and OKT4 lymphocytes. Electromyographic studies showed severe waxing by repeated stimulations (200% by 10 Hz; 330% by 20 Hz), very low M wave amplitude by single stimulation, and post-tetanic exhaustion. An Eaton-Lambert-type neuromuscular transmission block was thus thought to exist. Concentric needle electromyography showed a neurogenic pattern. The sensory and motor nerve conduction velocity was delayed. Microscopic examination of biopsied skeletal muscle showed neurogenic change. A sural nerve biopsy specimen showed a decrease in the number of myelinated fibers (fiber density 4333/mm2), segmental demyelination, remyelination, and mild axonal change. Thymectomy was performed and pathological examination showed invasive thymoma of predominantly the epithelial type. His muscular weakness and sensory disturbance improved gradually after thymectomy. On the postoperative immunological examination, serum IgG, gamma-globulin, OKT3 and OKT4 lymphocytes were normalized. On the other hand, OKT8 lymphocytes were increased and the OKT4 to OKT8 ratio was decreased. The electromyographic studies showed no waxing, normal M wave amplitude, and no post-tetanic exhaustion. Therefore, we consider that an Eaton-Lambert-type neuromuscular transmission block and sensorimotor neuropathy in this case were caused by the immunological abnormality accompanying malignant thymoma.     

Familial bulbo-spinal muscular atrophy associated with testicular atrophy and sensory neuropathy (Kennedy-Alter-Sung syndrome). Autopsy case report of two brothers

Autopsy cases of two brothers with bulbo-spinal muscular atrophy associated with gynecomastia, testicular atrophy and sensory neuropathy are reported. The disease started with finger tremor, proximal muscle weakness and facial muscle twitching at the second and fourth decades, accompanied by bulbar signs and glove-stocking type sensory disturbance. Systemic neurogenic patterns and diminished sensory nerve action potential amplitudes were recorded by electrophysiological studies. A marked loss of myelinated fibers was noticed upon sural nerve biopsy. Gonadal hormone values were normal, except for elevated urinary estrogen. Postmortem examinations revealed a remarkable degeneration of the facial and hypoglossal nuclei, and the spinal cord motoneurons. The skeletal muscles and the tongue showed neurogenic muscular atrophy with fatty replacement. Testicular atrophy was prominent showing hyalinized seminiferous tubuli with nodular and diffuse Leydig cell hyperplasia, containing estrogen immunoreactive substance. These clinical and histological features seemed to be highly compatible with those of Kennedy-Alter-Sung type bulbo-spinal muscular atrophy. The involvement of sensory peripheral nerves, however, was a distinct feature of this family.     

Hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy: report on a family

We describe two siblings affected by a motor and sensory neuropathy starting in childhood. Already in infancy, a spastic gait disturbance had become obvious, leading later to multiple surgical interventions. In adolescence, progressive loss of vision developed. At the time of our examination, both siblings showed severe weakness and atrophy of the distal muscles of legs and arms. Tendon jerks were brisk in proximal muscles; in the lower extremities, muscle tone was increased. Visual acuity was severely decreased. Nerve conduction studies revealed an axonal degeneration. This finding was confirmed by evaluation of a sural biopsy specimen in one patient, showing only few remaining myelinated fibres without signs of demyelination. This combination of hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy shows features of both hereditary motor and sensory neuropathy V and VI according to the classification of Dyck, indicating that these subtypes may not represent distinct entities. Received: 24 February 1997 Received in revised form: 30 May 1997 Accepted: 26 July 1997     

Motor Axonal Neuropathy During Treatment With Simvastatin

Simvastatin is a cholesterol-lowering drug that acts by inhibiting hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Abnormal laboratory findings include transient increases in serum creatine kinase (CK) due to a myopathic syndrome. Rarely, neurological side effects include axonal sensory-motor peripheral neuropathy, characterized in some cases by a prevalent motor involvement accompanied by subclinical sensory damage. We report a case of purely motor axonal neuropathy associated with simvastatin. A 72-year-old woman, after five years of treatment with simvastatin, developed progressive weakness, cramps and fasciculations mainly involving proximal muscles in the lower limbs, though without sensory symptoms or signs. Deep reflexes were lost in the lower limbs. There was no sign of upper motor-neuron involvement. CK was elevated (up to 2000 U/l). EMG showed marked neurogenic damage with fibrillations and fasciculations in the lower limbs. ENG showed motor fiber loss within the lower limb nerves without involvement of sensory fibers. CSF examination was normal. Deltoid muscle biopsy showed neurogenic changes and some ragged-red fibers. One year after simvastatin withdrawal the patient's state of weakness improved and the cramps resolved. The CK level dropped to 700 U/l.     

Mitochondrial myopathy with peripheral neuropathy]

This paper reported mitochondrial myopathy with peripheral neuropathy of 2 cases. Both patients were males. Age: 22, 32. Duration: 11, 14 years respectively. They showed recurrent paralysis and asthenia of limbs. Case 1 was motor sensory neuropathy, whose EMG revealed neurogenic injury. Case 2 involved only the lower limbs, whose lactic acid level was increased. In both patients, muscle biopsy showed Ragged Red fibers and abnormal mitochondria. Sural nerve biopsy revealed moderate reduction in the number of mylinated fibers and chronic axonal degeneration without regeneration cluster and hypertrophic neuropathy. Electron microscopic examination showed the increase of Schwann cells and mitochondria, and abnormal mitochondria being less marded in Case 2. Mitochondrial myopathy with peripheral neuropathy and its pathogenesis were discussed.     

Ulcero-mutilating neuropathy in an Austrian kinship without linkage to hereditary motor and sensory neuropathy IIB and hereditary sensory neuropathy I loci

OBJECTIVE: To elucidate genetic heterogeneity in ulcero-mutilating neuropathy. BACKGROUND: Ulcero-mutilating features and sensory loss have been observed in hereditary sensory neuropathy (HSN) and hereditary motor and sensory neuropathy (HMSN). HSN is characterized by marked distal sensory loss, frequent toe and foot ulcerations, osteomyelitis, and necrosis, which may be complicated by toe or limb amputations. Motor and autonomic nerve involvement can also occur to a variable degree. Recently, autosomal-dominant HSN type I was mapped to chromosome 9q22 in four families. In two other families with ulcero-mutilating neuropathy, a gene locus was assigned to chromosome 3q13-q22. Because motor symptoms were prominent in these latter two kinships, the disease was designated HMSN type IIB or Charcot-Marie-Tooth type 2B (CMT2B) neuropathy. METHODS: We report detailed clinical, electrophysiologic, and genetic data on a large Austrian family with ulcero-mutilating neuropathy, sensory loss, and amputations. RESULTS: Linkage analysis with chromosomal markers representing the HSN I and HMSN IIB loci excluded these gene loci in our family. CONCLUSIONS: These findings therefore indicate the existence of a third gene locus in autosomal-dominant inherited ulcero-mutilating neuropathies, showing that these neuropathies are genetically highly heterogeneous.     

Chronic axonal sensory and autonomic polyneuropathy without motor involvement: a new ‘chronic inflammatory neuropathy?’

We report the case of a woman with axonal sensory and autonomic neuropathy lasting several months who improved in association with steroid administration. During the course of her disease and in the follow-up, the patient underwent repeated cerebrospinal fluid (CSF) examinations, neurophysiological somatic, autonomic nervous system studies and sural nerve biopsy. Clinical and laboratory assessments demonstrated the occurrence of a monophasic, chronic sensory and autonomic neuropathy. A sural nerve biopsy suggested an axonopathy. After a progressive worsening of symptoms lasting about 6 months, steroid treatment was started and within 6 months a complete recovery, with normalization of the CSF findings, was observed. Although the 'chronic inflammatory neuropathies' are still debated entities, the features of this chronic, exclusively sensory and autonomic neuropathy are new, and the occurrence of a high protein level in the CSF, together with the favorable outcome associated with steroid treatment, suggests that our case might be another variant in this debated area.     

Nerve conduction and biopsy correlation in over 100 consecutive patients with suspected polyneuropathy

Neuropathy was classified physiologically and histologically as normal, axonal, demyelinative, or indeterminate using specific motor nerve conduction (NC) and sural sensory nerve biopsy (NB) criteria. Physiological and histological diagnoses were concordant in 63%, and minimally discordant in 14% of patients. The most important discordant patients were 6 with demyelinative neuropathy, 4 by NC, of which 2 were pure motor syndromes, and 2 by NB, both predominantly sensory syndromes. In the 55 patients with predominant axonal degeneration on biopsy, the extent of NC slowing was determined. As compound motor and sensory nerve action potential (CMAP and SNAP) amplitude declined, distal motor latency increased, whereas motor and sensory conduction velocity (CV) did not. Minimum F response latency increased as motor CV decreased, more in lower than upper extremity nerves. We conclude that: (1) except for sensory neuropathy, routine motor NC studies generally suffice in identifying demyelinative neuropathy; (2) NC slowing in axonal neuropathy is usually slight but may result in significantly prolonged distal motor latencies when CMAP amplitude is very low, and prolonged F wave latency when motor CV is slightly low; and (3) The physiologic criteria employed in this study rarely misclassifies neuropathy as demyelinative in patients with predominant axon loss on biopsy. © 1994 John Wiley & Sons, Inc.     

Amyloid-like IgM deposition neuropathy with multiple mononeuropathies and generalized neuropathy

Amyloid-like IgM deposition neuropathy is a distinct entity in the setting of IgM monoclonal gammopathy in which endoneurial perivascular entire IgM-particle accumulation leads to a painful sensory followed by motor peripheral neuropathy. We report a 77-year-old man presenting with progressive multiple mononeuropathies starting with painless right foot drop. Electrodiagnostic studies showed severe axonal sensory-motor neuropathy superimposed by multiple mononeuropathies. Laboratory investigations were remarkable for biclonal gammopathy of IgM kappa, IgA lambda and severe sudomotor and mild cardiovagal autonomic dysfunction. A right sural nerve biopsy showed multifocal axonal neuropathy, prominent microvasculitis, and prominent large endoneurial deposits of Congo-red negative amorphous material. Laser dissected mass spectrometry-based proteomics identified IgM kappa deposit without serum amyloid-P protein. This case has several distinctive features, including motor preceding sensory involvement, prominent IgM-kappa proteinaceous deposits replacing most of the endoneurium, a prominent inflammatory component, and improvement of motor strength after immunotherapy.     

Vitamin B1 deficiency polyneuropathy presenting homolateral imitative synkinesia]

We report a 56-year-old woman with vitamin B1 polyneuropathy, showing bilateral homolateral imitative synkinesia. Needle electromyogram revealed neurogenic changes, and the amplitude of muscle action potential was low. Sural nerve biopsy showed a marked loss of myelinated fibers, and severe axonal degeneration was diagnosed. Spinal and brain MRI revealed no abnormalities. In the literature, these synkinesias were observed in patients with parietal, thalamic, and basal ganglia lesions and with chorea. We suggest that this synkinesia is the release phenomenon in the circuit of the motor programming system due to the disturbance of peripheral nerve or funiculus posterior.