Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis

We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC.     

Human neurolymphomatosis in a patient with chronic lymphatic leukemia

A 62-year-old woman with chronic lymphatic leukemia (CLL) (RAI stage IV) with multiple organ involvement and diabetes mellitus, three months prior to death presented with a symmetrical sensory neuropathy of the upper extremities with little motor impairment and, two months later, sensory atactic neuropathy of the lower limbs. No cranial nerve or CNS impairment was noted. Clinical diagnosis was predominantly sensory neuropathy, but nerve conduction velocities were normal on upper limbs and moderately abnormal on lower limbs, the latter attributing to long lasting diabetes mellitus. The women died from acute subarachnoid hemorrhage. Autopsy revealed CLL of B-cell type with generalized organ involvement and acute craniospinal subarachnoid hemorrhage from ruptured cerebral aneurysm. There was selective neoplastic infiltration of the dorsal root ganglia and peripheral nerves, particularly the median nerve. Although selective infiltration of peripheral nerves by B-cell lymphoma cells was not associated with myelo-axonal degeneration, the relationship of this case to human neurolymphomatosis is discussed.     

Chronic relapsing multifocal sensory-motor neuropathy with conduction block

A 47 years old man had 13 episodes of relapsing and remitting sensory-motor neuropathy involving the upper limbs over the last 20 years. All but the last episode resolved spontaneously within 2 months. Neurophysiology revealed multifocal motor and sensory conduction block in the upper limbs with normal terminal latencies. CSF analysis was normal and anti-GM1 antibodies were not detected. There was a dramatic clinical improvement after intravenous immunoglobulin treatment. This case represents an unusual multifocal variant of chronic inflammatory demyelinating neuropathy.     

Churg Strauss syndrome during treatment of bronchial asthma with a leucotriene receptor antagonist presenting with polyneuropathy

Bronchial asthma can be associated with Churg Strauss syndrome (CSS). A peripheral neuropathy may be the initial manifestation of CSS. There is also some evidence that leucotriene receptor antagonists (LTAs) may trigger CSS in asthmatic patients, especially when steroids are tapered previously. However, the pathogenesis is unclear and the association between CSS and LTAs remains a matter of controversy. The aim of this report is to clarify this issue. A 79-year-old male patient with bronchial asthma for twenty years was admitted due to progressing gait disorder developing within the last two weeks. Asthma had been treated with a leucotriene receptor antagonist (Montelukast) for four years, as well as low doses of inhaled steroids and beta-2-agonists. On admission, neurological examination revealed a mild ataxia on both upper limbs and multifocal sensory disturbances without motor deficits. Nerve conduction velocity studies demonstrated normal results for the upper limbs and an axonal sensorimotor neuropathy of the lower limbs. Electromyography exhibited no spontaneous activity in the right tibialis anterior and rectus femoris muscle. Nerve-muscle biopsy revealed an eosinophilic vasculitis in both nerve and muscle. Laboratory examination showed leucocytosis and marked eosinophilia. A diagnosis of CSS was made. This case demonstrates a severe neuropathy in an asthmatic patient, during long lasting treatment with a LTA and continuous low doses of inhaled steroid, as the initial clinical feature of CSS.     

Novel mutations in the HSN2 gene causing hereditary sensory and autonomic neuropathy type II

Hereditary sensory and autonomic neuropathy type II (HSAN-II) is caused by recessive mutations in the HSN2 gene assigned to chromosome 12p13.33. The authors report three unrelated HSAN-II families with homozygous or compound heterozygous mutations resulting in the truncation of the HSN2 protein. Genotype-phenotype correlations indicated that HSN2 mutations are associated with an early childhood onset of a predominantly sensory neuropathy, complicated by acromutilations in both upper and lower limbs.     

Nerve conduction studies in spastic paraplegia,optic atrophy,and neuropathy (SPOAN) syndrome

Introduction: SPOAN (spastic paraplegia, optic atrophy, and neuropathy) syndrome is an autosomal recessive neurodegenerative disorder identified in a large consanguineous Brazilian family. Methods: Twenty‐seven patients with SPOAN syndrome (20 women), aged 4–58 years, underwent nerve conduction studies (NCS) of the median, ulnar, tibial, and fibular nerves, and sensory NCS of the median, ulnar, radial, sural, and superficial fibular nerves. Results: Sensory nerve action potentials were absent in the lower limbs and absent in >80% of upper limbs. Motor NCS had reduced amplitudes and borderline velocities in the upper limbs and absent compound muscle action potentials (CMAPs) in the lower limbs. Conclusions: The neuropathy in SPOAN syndrome is a severe, early‐onset sensory–motor axonal polyneuropathy. Normal NCS seem to rule‐out this condition. Muscle Nerve 49 : 131–133, 2014     

Childhood-onset multifocal motor neuropathy with conduction blocks

Multifocal motor neuropathy (MMN) is an acquired disorder with onset in adulthood. The authors describe a patient with a slowly progressing distal upper limb motor neuropathy since age 6 years, in whom definite conduction blocks in upper limbs, outside common entrapment sites, and no sensory involvement were consistent with MMN. IV immunoglobulin treatment produced marked muscle strength improvement and conduction block disappearance. MMN diagnosis should also be considered in childhood.     

An atypical case of mononeuritis multiplex in primary Sjogren's syndrome

We present an atypical case of peripheral nervous system (PNS) involvement in Sjogren's syndrome in a 63 year-old woman. Symptoms of an entrapment neuropathy were the first manifestation of the systemic disease and they were subsequently coupled to those of a mononeuritis multiplex. Clinical and laboratory signs for the diagnosis of Sjogren's syndrome became subsequently overt. The mononeuritis multiplex remained clinically limited to the upper limbs and characterized by unusually severe motor symptoms which progressed up to the development of a final complete deplegia. By contrast, sensory symptoms at the upper limbs remained mild over the entire course of the disease and the lower limbs revealed a subclinical sensory-motor damage only during the late stage.     

Peripheral neuropathy in cardiofaciocutaneous syndrome

A young adult male with cardiofaciocutaneous syndrome developed gait deterioration in childhood, with later evolution of distal wasting. His physical examination revealed intention tremor, distal weakness of the upper limbs with atrophy of the thenar, hypothenar, and interossei muscles, a wide-based gait, and large-fiber sensory loss in all limbs. Neuroimaging revealed stable mild chronic communicating hydrocephalus. Nerve conduction studies and electromyography demonstrated a moderately severe axonal neuropathy. The present case is, to our knowledge, the first reported case of peripheral neuropathy in association with cardiofaciocutaneous syndrome. The latter is a rare disorder, with significant comorbidities, in which a peripheral neuropathy may be under-recognized as a late cause of functional deterioration.     

Cutaneous silent period in human immunodeficiency virus-related peripheral neuropathy

The aim of this work was first to determine whether the cutaneous silent period (CSP), a marker of small-nerve-fibre function, was altered in human immunodeficiency virus (HIV)-positive subjects with predominantly sensory symmetrical polyneuropathy and, second, to assess whether such alterations were predictive of an impairment in the largest calibre sensory and motor nerve fibres of the upper limb (UL) peripheral nerves. CSP was assessed in three groups of subjects: healthy control subjects, HIV-positive subjects with peripheral neuropathy (PN) of the lower limbs, and HIV-positive patients with clinical and neurophysiological involvement of the four limbs. CSP study showed a significant increase of the latency compared to the controls both in HIV-positive cases with no impairment in the UL (p=0.006) and in patients with four-limb neuropathy (p=0.002). CSP study in HIV-positive patients with mild lower limb distal sensory polyneuropathy can detect an early involvement of the UL peripheral nerves. CSP latency increase could therefore be addressed as the first sign of PN spreading to the UL.     

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.     

ACUTE PREVALENTLY MOTOR AXONAL NEUROPATHY DURING DISULFIRAM TREATMENT

Disulfiram (Di) presents hepatic and central nervous system toxicity as main side effects. Di occasionally produces peripheral neuropathy consisting of a chronic axonal sensory pattern. A 34‐year‐old woman, after a five‐year history of moderate abuse, started Di therapy (400 mg per day) and stopped alcohol intake. Three months later, painful tingling and burning sensation occurred on distal lower limbs, rapidly followed by a foot drop within three days and severe weakness spreading to proximal segments and to upper limbs within two weeks. The patient presented with moderate distal multimodal hypoaesthesia, complete loss of deep tendon reflexes, mild distal muscle hypotrophy and severe motor disability (Rankin grade 4). Electrophysiological examination showed a typical prevalently motor axonal neuropathy with inexcitability of motor responses in lower limbs, but normal latencies of “F” responses in upper limbs. Standard cerebrospinal fluid (CSF) examination was normal and investigations for cytomegalovirus, herpes viruses and Campylobacter Jejuni (CJ) were negative. Anti GM1 antibodies (Ab) were negative in serum and CSF. Sural nerve biopsy revealed axonal degeneration with moderate loss of large myelinated fibres, frequent endoneurial foamy macrophages and milder degeneration of unmyelinated axons. No axonal swellings with filamentous deposits were detected. Rows of myelin ovoids were present on teased fibres, whereas rare short remyelinated internodes and no segmental demyelination were observed. Follow‐up, three months later, shows a significant increase of general strength and sensory function (Rankin grade 3), though heels and toes gait is not recovered and painful/burning paraesthesias still require gabapentin treatment. The main diagnostic problem of this case is distinction from acute axonal Guillain Barré syndrome. Although there is no consensus regarding electrophysiological diagnostic criteria for AMSAN, significant abnormalities of “F” waves are generally observed on affected nerves. On the immunological side, anti GM1 Ab increased titer and evidence of CJ infection, though not mandatory, are very frequent in AMSAN. Moreover, pathological changes distinctive of AMSAN, such as peri‐axonal or intra‐axonal macrophages, were absent in our case. On the other hand, a similar acute onset of a sensory—motor axonal neuropathy during Di treatment has been previously described (Nukada, 1981).     

Enlarged, multifocal upper limb neuropathy with HTLV-I associated myelopathy in a patient with chronic adult T-cell leukemia

The authors herein describe a case of multifocal peripheral neuropathy with HTLV-I-associated myelopathy (HAM) in a patient with chronic adult T-cell leukemia (ATL). The clinical features included subacute progressive sensory-motor neuropathy in the bilateral upper limbs, and bilateral pyramidal tract involvement with bladder dysfunction. An MRI with (67)gadolinium enhancement revealed enlargement of the affected peripheral nerves. (8)FDG positron emission tomography (PET) disclosed increased uptake in the affected nerves, suggesting neurolymphomatosis or inflammation. Anti-HTLV-I antibody was positive in both the serum and CSF. The HTLV-I proviral load in the peripheral blood mononuclear cells was high. Chemotherapy for ATL resulted in marked improvement of motor functions in the upper limbs. This is the first case of multifocal upper limb neuropathy with HAM in a patient with chronic ATL.     

Chronic ataxic neuropathy initially diagnosed as ataxic variant of guillain barré syndrome

Aquadynia is a rare phenomenon of water‐induced pain through presumed neural mechanisms. We describe two women in whom bathing was regularly followed by pain in the lower limbs, as a unique symptom (case 1) and, respectively, in the clinical context of an axonal polyneuropathy (case 2). Case 1: A 71‐year‐old woman complained, by age 69, of pruritus and pinprick‐like pain in the extremities that lasted about 20 minutes following bathing. Neurological examination and electroneurography were negative, as well as investigations for systemic diseases. Quantitative sensory testing (QST) showed abnormal cold‐pain sensation. Treatment with gabapentin was not effective. Case 2: A 69‐year‐old woman affected with HCV‐related cryoglobulinemia had numbness and aquadynia in the distal lower limbs and restless legs syndrome, in the last few months. Neurological examination showed absent ankle jerks, and decreased touch and vibration sense in the feet. Electroneurography demonstrated an axonal neuropathy. Aquadynia likely represents a manifestation of small fiber neuropathy. It is unclear whether it has to be viewed as a primary sensory phenomenon similar to allodynia, or a type of noradrenergic pain primarily due to autonomic dysfunction. Alteration of QST in case 1, and the association with obvious features of sensory neuropathy in case 2, may favour the sensory hypothesis.     

A case with HTLV-I associated myelopathy (HAM) accompanied by primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH)]

We reported a 60-year-old female patient with HTLV-I associated myelopathy (HAM) accompanied by primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). The diagnosis of PBC and AIH was confirmed by liver biopsy. HAM is considered to be mediated by cellular immune mechanisms, while humoral immune mechanisms may play a predominant role in the development of PBC and AIH. Flowcytometric analysis of lymphocyte subset of peripheral blood was within normal limits. We then collected CD4 positive cells from the patient. These cells expressed T helper 2 (Th 2) cytokine mRNA such as IL-4 and IL-10, but did not express Th 1 cytokines, indicating the predominance of Th 2 in this patient. This case suggested the possibility that disease associated Th 2 might develop in the course of Th1-mediated disease like HAM.     

Two distinct types of neuropathy associated with Sj?gren's syndrome developed in one patient. The importance of the selection of an appropriate therapeutic regimen]

A 62-year-old woman was admitted to our hospital because of muscle weakness and sensory disturbance in extremities. She showed weakness, muscle atrophy and sensory abnormality in four limbs with patchy distribution, suggesting involvement of multiple peripheral nerve trunks. Serum titers of anti-SS-A, SS-B, and antinuclear antibody were elevated. Sural nerve biopsy showed recanalization and lymphocytic infiltration in the epineural small vessels, suggesting the presence of vasculitis. She was diagnosed as having vasculitic neuropathy complicated with Sj?gren's syndrome. Methylprednisolone pulse therapy followed by oral prednisolone was started and these symptoms gradually improved in one month. At age 63, she felt dysesthesia in the right lower limb and this sensory abnormality spreaded to upper limbs. Two years later, she was admitted again due to clumsiness of hands and gait disturbance. Neurological examination showed decreased vibration and position sense of lower limbs and limb ataxia in addition to dysesthesia. Electrophysiological studies demonstrated significant decrease in amplitude of sensory nerve action potentials and delayed somatosensory evoked potentials after N13, indicating impairment of dorsal root ganglions. She was treated with intravenous immunoglobulin (400 mg/kg, total 15 g/day) for 5 days. One week later, sensory ataxia was improved. It has been known that Sj?gren's syndrome is often complicate with various types of neuropathies including vasculitic neuropathy and sensory neuropathy. Our patient developed these two different types of neuropathies which were dramatically improved after two different therapeutic regimens; indicating the importance to select a suitable treatment regimen in accordance with the mechanism of neuropathy associated with Sj?gren's syndrome.     

Phenotypic heterogeneity in hereditary motor neuropathy type V: a new case report series

Previous studies have revealed a wide phenotypic heterogeneity in hereditary motor neuropathy type V in which upper and lower motor neurons and peripheral motor axons are variously affected, even within the same family. In this case series, we describe the genetic, clinical and electrophysiological features of patients belonging to a four-generation Italian family. Because of a possible anticipation phenomenon, the disorder became apparent at an earlier age as it passed to the next generation, with a median age of onset of 65?years for the first 2 generations, 32 for the third, and 13.5 for the fourth. The symptoms at onset varied considerably among the sufferers, with a predominant impairment of the hands in seven cases, the impairment of the four limbs in one patient and only of the lower limbs in another. Also muscle atrophy was variable, from very mild to severe (wasting of the distal muscles of the limbs). Moreover, electrophysiological results were heterogeneous, including cases with isolated and with diffuse axonal motor neuropathy, and one case of motor sensory polyneuropathy. A novel polymorphism G→T was also found in the Berardinelli-Seip congenital lipodystrophy 2 gene on intron 4. This broad phenotypic and genotypic spectrum calls the clinician attention to this rare and still insufficiently known disease.     

11 cases of neuropathy induced by almitrine, of which one had optic neuropathy

The only etiologic factor retained in 11 patients with sensory or sensory-motor neuropathy was almitrine therapy. In one patient there was in addition an optic neuropathy. The reduction in visual acuity in this patient coincided with the onset of the sensory-motor neuropathy of lower limbs after treatment with 100 mg/day of almitrine over a 2-year period. No other metabolic, inflammatory, toxic, vascular or immunologic cause was found. There was a moderate chronic respiratory insufficiency. Visual recuperation started one month after the arrest of almitrine treatment and was satisfactory 7 months later. The other 10 patients had neuropathy of limbs without visual disorders. Neuromuscular biopsy in one case showed lesions to be of the axonal type.     

A case of hereditary motor and sensory neuropathy of neuronal type with retardation of motor development

An atypical case of hereditary motor and sensory neuropathy of neuronal type with retardation of motor development was described. The patient was a 15-year-old boy who had suffered from distal muscle weakness with atrophy of four limbs and deformities of hands and feet since age 6 months. These symptoms were slowly progressive. He had never walked. His parents were not consanguinous. His parents and two siblings were unremarkable on neurological examination and on nerve conduction studies. On neurological examination, he showed severe degree of muscle weakness and atrophy in the distal upper and lower limbs, moderate degree of muscle weakness and atrophy in the proximal upper limbs and slight degree of made weakness and atrophy in the proximal upper limbs. Deep tendon reflexes in four limbs were decreased or absent. Vibration sensation was moderately decreased in the distal parts of four limbs. On the nerve conduction studies, no sensory nerve potential was recorded in the median, ulnar and sural nerves bilaterally. Motor nerve conduction velocity of the right tibial nerve was 21 m/sec and the amplitude of the compound muscle action potential (M-wave) was 0.15 mV, and no M-wave was elicited with the electrical stimulation of the median, ulnar and peroneal nerves. Neelde EMG showed fibrillation potentials and giant spikes with a reduction of the number of motor units. On sural nerve biopsy, the densities of both myelinated and unmyelinated fibers were severely decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

一氧化二氮滥用致周围神经病患者的神经电生理特点

目的探讨一氧化二氮(N_2O)滥用致中毒性周围神经病患者的神经电生理特点。方法回顾性分析10例N_2O滥用导致的周围神经病患者的神经电生理(神经传导速度测定、针极肌电图检查、F波、H波)特点。结果与正常参考值相比,上、下肢近端所检运动纤维及上、下肢远端所检运动纤维异常率分别为0、40%、37.5%、90%,异常运动纤维远端潜伏期(MLAT)分别延长0、36.1%、17.8%、37.2%,复合肌肉动作电位(CMAP)分别下降0、88.6%、31.4%、64.5%;上、下肢远端运动纤维运动传导速度测定(MCV)分别延长10.4%、16.4%;上、下肢远端感觉纤维异常率分别为7.5%、80%;上、下肢异常感觉纤维波幅分别下降7.5%、79.4%,感觉传导速度测定分别延长0、8.6%;上、下肢F波异常率分别为0、50%;双下肢H波异常率100%;双上肢针极肌电图异常率30%,双下肢针极肌电图异常率90%(P<0.05)。结论N2O滥用致周围神经损害可同时累及运动纤维与感觉纤维,以轴索损害为主,下肢受累为著,远端受累较近端受累为重,具有长度依赖性及对称性。针极肌电图可早期出现中-多量失神经电位,大力收缩募集减少,伴或不伴运动单位时限增宽。神经电图提示F波出现率减少或H波波幅降低,伴或不伴潜伏期延长。