Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation

Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy.     

Hereditary neuropathy with liability to pressure palsy (HNPP) in childhood: a case study emphasizing the relevance of detailed electrophysiological examination for suspected HNPP in the first decade

Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder characterized by recurrent mono-neuropathies secondary to minor trauma or compression. Whilst typical episodes of palsy generally become apparent during the second and the third decades, HNPP is rarely diagnosed in the first decade. We present the case of a 6-year-old patient to draw attention to the possibility of HNPP attacks in the first decade and the importance of detailed electrophysiological examination.     

Leber's Hereditary Optic Neuropathy with Olivocerebellar Degeneration due to G11778A and T3394C Mutations in the Mitochondrial DNA

Background

Leber''s hereditary optic neuropathy (LHON) is a mitochondrial disorder with optic nerve atrophy. Although there are no other associated neurological abnormalities in most cases of LHON, cases of "LHON plus" have been reported.

Case Report

The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations.

Conclusions

These results suggest that the combination of G11778A and T3394C mutations leads to an atypical LHON phenotype.     

Posterior antebrachial cutaneous nerve conduction study in radial neuropathy

Radial neuropathy most commonly occurs as a result of external compression at the spiral groove region. The posterior antebrachial cutaneous nerve (PACN) conduction study was performed in 15 consecutive patients with radial palsy. Unilateral PACN abnormalities were present in 11 patients. A normal PACN study was correlated with clinical improvement at 3 months. Conversely, PACN abnormality was correlated with radial motor axon loss and a poorer prognosis. The PACN study is a simple adjunct which provides additional information relating to the diagnosis and prognosis of radial lesions.     

“Sunbath polyneuritis”: Subacute axonal neuropathy in perazine-treated patients after intense sun exposure

This article aims at drawing attention to the peculiar association of intense exposure to sunlight and subacute development of sensory neuropathy which was seen in 7 psychiatric patients treated with the phenothiazine derivative, perazine. Three patients additionally developed bilateral VII nerve palsy. Symptoms followed a monophasic course with almost complete remission. Routine neurophysiology suggested axonal neuropathy confirmed by sural nerve biopsy in 1 patient. A toxic origin of neuropathy is supposed, possibly induced by phenothiazine photoproducts, which may cause cell damage via lipid peroxidation. © 1996 John Wiley & Sons, Inc.     

Distal and scapuloperoneal distributions of muscle involvement occurring within a family with type I hereditary motor and sensory neuropathy

Summary Davidenkow's syndrome has been defined as a hereditary disorder characterized by proximal muscle weakness and wasting in the upper limbs with distal weakness in the lower, and associated with distal sensory loss in all four limbs. It has been assumed to be genetically distinct. A family is described in which the index case displayed these features. Motor nerve conduction velocity was substantially reduced. Another member displayed distal motor and sensory involvement in both upper and lower limbs and thus conformed to the clinical pattern of the hypertrophic form of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). A third member was somewhat intermediate, with generalized upper limb and distal lower limb weakness. It is concluded that Davidenkow's syndrome is not genetically distinct and that it may occur as a phenotypic manifestation of type I hereditary motor and sensory neuropathy.

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Zusammenfassung Davidenkow's Syndrom wird als eine Erbkrankheit definiert, welche charakterisiert ist durch eine proximale Muskelschwäche und zunehmende motorische Behinderung der oberen Extremitäten mit distaler Schwäche der unteren, zugleich mit distalen Sensibilitätsstörungen aller vier Gliedmaßen. Es wurde angenommen, daß es sich genetisch um eine wohldefinierte eigene Erkrankung handelt. Es wird eine Familie beschrieben, in welcher der Propositus die oben erwähnten Merkmale aufwies. Die motorische Erregungsleitungsgeschwindigkeit war wesentlich verlangsamt. Ein anderes Glied der Sippe zeigte einen motorischen und sensiblen Befall aller vier Extremitäten und entsprach klinisch der hypertrophischen Form der Charcot-Marie-Toothschen Krankheit (hereditäre motorische und sensorische Neuropathie von Typ I). Ein drittes Glied der Sippe nahm eine intermediäre Stellung ein mit generalisierter Schwäche der oberen Extremitäten und einer distalen Schwäche der unteren. Es wird deshalb gefolgert, daß Davidenkow's Syndrom kein genetisch einheitliches Krankheitsbild ist und daß es als phänotypische Manifestation einer hereditären motorischen und sensorischen Neuropathie vom Typ I auftreten kann.

     

Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis

A 56-year-old male with recurrent painless focal neuropathies and a family history of peripheral neuropathy of unknown etiology presented with progressively worsening of impaired sensations and weakness in his lower extremities. His initial electrodiagnostic evaluation was suggestive of severe sensory and motor peripheral polyneuropathy. The genetic testing was performed for familial causes of peripheral neuropathy as there was a family history of peripheral neuropathy of unknown etiology. The patient was found to have 1.5-Mb deletion in the PMP22 gene which was confirmatory of hereditary neuropathy with liability to pressure palsies (HNPP). He developed progressive upper and lower extremity weakness, bulbar dysfunction and widespread fasciculations during the course of his illness. He was subsequently diagnosed with amyotrophic lateral sclerosis (ALS). This is the second reported case of HNPP associated with ALS. We discuss significant clinical and electrodiagnostic findings of this interesting case.     

Hereditary neuropathy with liability to pressure palsies (HNPP) in a toddler presenting with toe-walking, pain and stiffness

The typical clinical presentation of hereditary neuropathy with liability to pressure palsies is an adult-onset recurrent, painless monoparesis. Electrophysiological abnormalities - decreased nerve conduction velocities and delayed distal latencies - can be detected even in asymptomatic patients. We describe a toddler, who presented with asymmetric toe walking, painful cramps and stiffness in the legs. He had calf hypertrophy, brisk tendon reflexes and bilateral Babinski signs and the electrophysiological examination was normal. The unlikely diagnosis of hereditary neuropathy with liability to pressure palsies was reached 5 years later, when the boy started to complain of episodic numbness and weakness in the upper extremities. His father, paternal aunt and grandmother had similar symptoms, but they had never been investigated. The typical 1.5 Mb deletion on chromosome 17p11.2–12 was found in our patient and his affected relatives.     

Focal posterior interosseous neuropathy in the presence of hereditary motor and sensory neuropathy,type I

A 30-year-old male with hereditary motor and sensory neuropathy, type I (HMSN I), presented with asymmetric weakness of finger extension and radial deviation with left wrist extension, previously felt to be a manifestation of the peripheral neuropathy. Nerve conduction studies confirmed HMSN I; however, needle EMG revealed marked, ongoing axonal loss in muscles innervated by the left posterior interosseous nerve (PIN) only. At surgery there was focal fusiform swelling in the PIN at exit from the supinator muscle, compatible with localized hypertrophic neuropathy, which has not been reported before in HMSN I. A concomitant focal mononeuropathy should be considered in cases of hereditary neuropathy with marked asymmetry of weakness. © 1996 John Wiley & Sons, Inc.     

Hallazgos clínico-neurofisiológicos en neuropatías hereditarias sensibles a la presión con deleción del cromosoma 17p11.2

IntroductionHereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported.MethodsWe retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016.ResultsIn addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%).ConclusionOur results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.     

Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent sensory or motor manifestations. The molecular basis of HNPP is a deletion on chromosome 17p11.2. We studied a family (father, 61 years; mother, 55 years; 6 children of mean age 25.3 years) showing symptoms of carpal tunnel syndrome in 4 members (the parents and 2 sons). No one of them reported episodes of nerve palsy. In all the patients, except the mother and the younger son, electrophysiologic evaluation showed a sensorimotor polyneuropathy with delayed sensorimotor latencies. Genetic analysis was carried out in the parents and the eldest son. The 17p11.2 deletion was detected in the father and son, indicating paternal transmission of the disease. Clinical manifestations of HNPP may be atypical. Sometimes there is no history of acute nerve palsy, as in this family. For this reason, the frequence of HNPP might be underestimated. Electrophysiological examination is of great importance for the diagnosis of HNPP. Genetic analysis is a rapid and reliable diagnostic tool that can be combined with simplified electrophysiological examination, avoiding the need for nerve biopsy. In conclusion, the diagnosis of HNPP should be invoked in early onset entrapment neuropathies. Received: 8 November 2002 / Accepted in revised form: 28 March 2003 Correspondence to: R. Del Colle     

Incidence of common compressive neuropathies in primary care

Apart from carpal tunnel syndrome, there are no population based studies of the epidemiology of compressive neuropathies. To provide this information, new presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed. The study revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were: carpal tunnel syndrome, men 87.8/women 192.8; Morton's metatarsalgia, men 50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica, men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New presentations were most frequent at ages 55-64 years except for carpal tunnel syndrome, which was most frequent in women aged 45-54 years, and radial nerve palsy, which was most frequent in men aged 75-84 years. In 2000, operative treatment was undertaken for 31% of new presentations of carpal tunnel syndrome, 3% of Morton's metatarsalgia, and 30% of ulnar neuropathy.     

The first Japanese case of Charcot–Marie–Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation

Charcot–Marie–Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating neuropathy. It presents as infancy or early childhood-onset neuropathy associated with FGD4 mutations. Clinically it causes predominantly distal muscle weakness. On nerve biopsy examination, myelin outfoldings are seen. The previous case reports have been from regions bordering the Mediterranean, as well as a family from Northern Ireland. This paper presents the detailed clinical course of the first reported case of CMT4H in a Japanese woman. The patient showed mild weakness without scoliosis and a severe sensory disturbance; her functional impairment was less severe than the previously published cases. In addition, a novel homozygous FGD4 c.837-1G>A mutation was identified in this patient.     

Magnetic resonance imaging findings in bilateral Bell's palsy.

Bell's palsy (idiopathic facial paralysis) is the most common cause of unilateral peripheral facial neuropathy. Bilateral involvement occurs in less than 10% of cases. The authors describe a 20-year-old man with bilateral idiopathic facial weakness. Brain magnetic resonance imaging (MRI) showed abnormal bilateral enhancement of the proximal intracanalicular segments of VII/VIII nerve complexes. The enhancement was most prominent in the leptomeningeal regions. There was no facial nerve swelling. Three months later he had improving residual bifacial weakness. To the authors' knowledge, this is the first report of abnormal MRI findings in bilateral Bell's palsy.     

Varying occurrence of vocal cord paralysis in a family with autosomal dominant hereditary motor and sensory neuropathy

A white British family with the axonal form of hereditary motor and sensory neuropathy (HMSN, type II) contained one member who developed a recurrent laryngeal nerve palsy at the age of 41 years, in addition to 4 years of symptomatic polyneuropathy and an abducens nerve palsy. Neither of the other family members (the mother and sister) with electrophysiologically confirmed polyneuropathy had any neuropathic symptoms in the limbs or laryngeal or respiratory muscle involvement. An autosomal dominant pattern of inheritance is likely. This is a second report of this rare form of HMSN (type IIC) in which there is associated laryngeal or respiratory muscle weakness. This family differs from the two previously reported pedigrees in which laryngeal or diaphragm weakness had commenced within the first two decades. The discovery of asymptomatic family members attests to the diagnostic value of clinical and electrophysiological study of first-degree relatives when laryngeal or bulbar symptoms develop in the context of chronic axonal polyneuropathy. HMSN type IIC should be distinguished from the more common forms of HMSN – type IIA, in which axonal polyneuropathy is restricted to the limbs, and type IIB, which is of early onset and associated with foot ulceration. Received: 10 July 1998 Received in revised form: 8 December 1998 Accepted: 10 December 1998     

A case of multiple cranial neuropathy with positive antinuclear antibody responded to steroid]

A 56-year-old woman was admitted to our hospital because of bilateral ptosis, total ophthalmoplegia, bilateral facial palsy and left hypoglossal nerve palsy. Antinuclear antibody (ANA) showed high titer of 1280 but other data were normal. With oral prednisolone therapy (40 mg/day), the symptoms improved gradually but ANA titer did not show any significant change. We thought multiple cranial neuropathy of the patient was due to autoimmune disease such as collagen disease or cranial nerve type of Guillain-Barré syndrome from her symptoms and positive ANA. In contrast to other reported cases of multiple cranial neuropathy with positive ANA, in our patient ANA titer was high, only motor cranial nerves were impaired, and total ophthalmoplegia was found. Steroid therapy was useful in accordance with other reports. Although our patient has no symptoms related to collagen diseases, a long follow-up of this patient is considered to be necessary.     

AAEE case report #20: hereditary motor and sensory neuropathy, type I

A case study is reported regarding a 32-year-old man with classic clinical and electrophysiologic features of hereditary motor and sensory neuropathy, type I (HMSN I), a slowly progressive autosomal dominant condition marked by slow motor and sensory velocities and generalized segmental demyelination. Another clinically similar autosomal dominant neuropathy (HMSN II) is distinguished from HMSN I by nearly normal nerve conduction velocity. Acquired demyelinating neuropathy may occasionally resemble HMSN I clinically, but the former demonstrates electrophysiologic features not seen in the latter such as conduction block, dispersed compound muscle action potentials, and differential slowing of conduction velocity. Neuropathologic studies of HMSN I suggest that both neuronal and Schwann cell distrubances play a role in pathogenesis.     

Friday night palsy: an unusual case of brachial plexus neuropathy

Brachial plexopathy can result from traction injury, radiation injury, local or metastatic cancer, hereditary, or idiopathic causes. However, brachial plexopathy resulting from malposition of an arm during sleep, similar to Saturday night palsy, has not been reported. We report a case of brachial plexus neuropathy that occurred after the patient slept on his shoulder and arm following excessive alcohol consumption on a Friday night.     

Concurrence of Multifocal Motor Neuropathy and Hashimoto's Thyroiditis

Background

Multifocal motor neuropathy (MMN) is an immune-mediated disorder that is characterized by slowly progressive and asymmetrical weakness, but its pathophysiological mechanism is uncertain. The hypothesis that MMN is an immunological disease has been supported by the proven therapeutic effects of intravenous immunoglobulin and the detection of antiganglioside antibodies in MMN patients. The coexistence of MMN with other immune diseases has been rarely reported.

Case Report

A 37-year-old woman visited our hospital complaining of weakness in both hands. The clinical manifestations coincided well with MMN: predominantly distal upper-limb weakness, asymmetric involvement, a progressive course, absence of sensory symptoms, absence of pyramidal signs, and sparing of the cranial muscles. The electrophysiological findings also supported a diagnosis of MMN, with motor nerve conduction block in the median, ulnar, and radial nerves, without sensory nerve involvement. The patient was simultaneously diagnosed as having Hashimoto''s thyroiditis, which is a well-known immune-mediated disease.

Conclusions

The concurrence of MMN and Hashimoto''s thyroiditis in our patient is significant for understanding the immunological characteristics of the two diseases.     

Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India

Aims:

To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center.

Settings and Design:

A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present.

Results:

The frequency of auditory neuropathy spectrum disorder was 1.12%. Sixty percent were found to have neurological involvement. This included cerebral palsy in children, peripheral neuropathy (PN), spinocerebellar ataxia, hereditary motor-sensory neuropathy, spastic paresis, and ponto-bulbar palsy. Neurological lesions did not present simultaneously with hearing loss in most patients. Sixty-six percent of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages.

Conclusions:

There is a high prevalence of neurological lesions in auditory neuropathy spectrum disorder which has to be kept in mind while evaluating such patients. Follow-up and counselling regarding the appearance of neuropathies is therefore important in such patients. A hereditary etiology is indicated in a majority of cases of auditory neuropathy spectrum disorder.