HyperIgEaemia in patients with juvenile muscular atrophy of the distal upper extremity (Hirayama disease)

BACKGROUND: Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is characterised by anterior horn cell loss in the lower cervical cord, presumably caused by anterior displacement of the dural sac during neck flexion. A recent report suggests that atopy and IgE may contribute to anterior horn damage. OBJECTIVE: To investigate whether IgE is a contributing factor in Hirayama disease. METHODS: Serum total IgE and allergen specific IgE were examined in 20 consecutive patients, and their correlations with clinical profiles investigated. RESULTS: Past or present history of allergy/atopy was found in only four patients (20%), but serum IgE was raised in 14 (70%). Patients with hyperIgEaemia had more severe clinical disabilities than those without (p = 0.01). In patients whose history of Hirayama disease was less than five years, serum total IgE was higher than in those with the disease for five years or more (p = 0.05). CONCLUSIONS: The results suggest that hyperIgEaemia is often associated with Hirayama disease and can facilitate its pathophysiology, particularly in the early phases of the disease. HyperIgEaemia does not appear to involve the anterior horn cells primarily.     

Chronic unilateral distal juvenile muscular atrophy localized to the upper extremity (Hirayama type). A European case

A 40 year-old Frenchman had had for 12 years, an amyotrophy of one upper limb. Clinical features were similar to those previously reported in Japan and India i.e. atrophy limited to one hand and forearm, with mild functional discomfort, and slow progression for 2 years after which the disorder did not progress. Electromyography showed disturbances of anterior horn cell type. The cause of this syndrome is unknown, no pathological case has yet been reported. The prognosis appears to be good.     

Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity

OBJECTIVE: To investigate specificity and significance of dynamic changes of the cervical dural sac and spinal cord during neck flexion in juvenile muscular atrophy of the distal upper extremity. BACKGROUND: The disorder affects young people-predominantly men-and is progressive for several years. One autopsy case showed ischemic necrosis of the cervical anterior horn, suggesting that the disorder is a type of cervical myelopathy. Some authors classify it as monomelic amyotrophy, implying that it is a focal motor neuron disease. METHODS: Neuroradiologic examinations including myelography, CT myelography, and MRI in a fully flexed neck position were performed on 73 patients with this disorder and on 20 disease control subjects. RESULTS: A distinctive finding in the disorder was forward displacement of the cervical dural sac and compressive flattening of the lower cervical cord during neck flexion. The forward displacement was significantly greater in patients with disease duration less than 10 years than in age-matched control subjects and patients in a late, nonprogressive stage. CONCLUSIONS: Radiologic abnormalities of the lower cervical dural sac and spinal cord support the hypothesis that this disorder is a type of cervical myelopathy.     

Juvenile muscular atrophy of distal upper extremity (Hirayama disease): Focal cervical ischemic poliomyelopathy

Hirayama disease is characterized by an initially progressive muscular weakness and atrophy of the distal upper limb(s) in adolescence, occurring predominantly in males, followed by spontaneous arrest within several years. Although the disease could be separated from motor neuron disease, some authors considered the illness to be a variant of degenerative motor neuron disease until the first autopsy case was reported which showed focal ischemic changes in the anterior horn of the lower cervical cord. Since then, many in Japan have recognized the disease as cervical ischemic poliomyelopathy; however, several authors in foreign countries did not or do not appreciate the pathologic findings of the disease, and still consider the illness a degenerative motor neuron disease. The pathology of the disease prompted neuroradiologic investigations, which have revealed dynamic changes of the cervical dural sac and spinal cord induced by neck flexion. The cause of these dynamic changes is unknown. However, as the number of patients is exceedingly large in Japan, there may be an ethnic factor.     

Cervical collar therapy for juvenile muscular atrophy of distal upper extremity (Hirayama disease): results from 38 cases]

BACKGROUND: Juvenile muscular atrophy of distal upper extremity is a peculiar type of cervical myelopathy affecting young people characterized by localized amyotrophy in the forearm and hand that is initially progressive, and then stabilized in a few years. The anterior horn cell damage may be induced by forward displacement of the lower cervical dural sac and spinal cord on neck flexion. We proposed that the forward displacement was one of pathogenic factors, and reported that therapeutic intervention using a cervical collar in order to minimize neck flexion halted the progressive weakness in some patients. OBJECTIVE: To examine effectiveness of cervical collar treatment for this disease and to investigate clinical and radiological profiles that predict a favorable outcome before treatment. METHODS: Thirty-eight patients who had progressive illness within 5 years after onset underwent cervical collar therapy (treatment group). Forty-five patients in a previous case series without any therapeutic intervention made up a control group. The duration of progressive phase of illness was compared between the two groups. In the treatment group, the time interval from onset and the measurements of cervical cord atrophy and its flattening on neck flexion at the introduction of treatment by CT-myelography or MRI were analyzed with respect to prognosis. RESULTS: All the patients in the treatment group showed no further progression after introduction of treatment. The duration of the progressive period was shorter in the treatment group (mean 1.8 +/- 1.2 years) than in the control group (mean 3.2 +/- 2.3 years) (p < 0.005). In the treatment group, 15 of 31 patients within 2.5 years after the onset showed not only stabilization but also improvement of muscular weakness or cold paresis. Five of 7 patients who had no or mild cord atrophy at the introduction showed improvement after treatment. CONCLUSION: Cervical collar therapy induces a premature arrest of this disease. Improvement is expected in patients who have shorter duration of illness and have mild cord atrophy in a neutral neck position. Early diagnosis and therapeutic intervention may minimize the functional disability of young patients.     

Clinical and radiological profile of Hirayama disease: A flexion myelopathy due to tight cervical dural canal amenable to collar therapy

Background:

Hirayama disease (HD) is benign focal amyotrophy of the distal upper limbs, often misdiagnosed as motor neuron disease. Routine magnetic resonance imaging (MRI) is often reported normal.

Objective:

To study the clinicoradiological profile of hand wasting in young males.

Materials and Methods:

Patients presenting with insidious-onset hand wasting from March 2008 to May 2011 were evaluated electrophysiologically. Cervical MRI in neutral position was done in 11 patients and flexion contrast imaging was done in 10 patients.

Results:

All patients were males less than 25 years of age, with median age 23 years, except one patient who was 50 years old. Duration of illness was 3 months to 3 years. All (100%) had oblique amyotrophy, four (36%) cold paresis, 10 (91%) minipolymyoclonus and three (27%) had fasciculations. Regional reflexes were variably absent. Two patients (18%) had brisk reflexes of lower limbs with flexor plantars. Electromyography (EMG) showed chronic denervation in the C7-T1 myotomes. Neutral position MRI showed loss of cervical lordosis in 10/11 (91%), localized lower cervical cord atrophy in 9/11 (82%), asymmetric cord flattening in 11/11 (100%) and intramedullary hyperintensity in 2/11 (18%); flexion study showed loss of dural attachment, anterior displacement of dorsal dura, epidural flow voids in 9/10 (90%) and enhancing epidural crescent in 10/10 (100%). Clinical profile, imaging and electrophysiological findings of the patient aged 50 years will be described in detail as presentation at this age is exceptional. Collar therapy slowed progression in most cases.

Conclusion:

Clinical features of HD corroborated well with electrophysiological diagnosis of anterior horn cell disease of lower cervical cord. While dynamic contrast MRI is characteristic, routine studies have a high predictive value for diagnosis. Prompt diagnosis is important to institute early collar therapy.     

Anterior shift of posterior lower cervical dura mater in patients with juvenile muscular atrophy of unilateral upper extremity

Myelography was performed in 16 male patients with juvenile muscular atrophy of unilateral upper extremity. The age at onset ranged from 11 to 19 years (average, 16 years), and the age at study ranged from 15 to 38 years (average, 25 years). The most remarkable finding was an anterior shift of lower cervical dural canal during neck flexion, particularly of its posterior wall at around 6th vertebral level. The above finding was clearly shown in 12 patients whose duration of illness was under 20 years but not in 4 patients whose duration of illness was 20 years or over. And the rates of anterior shift of posterior lower cervical dura mater was inversely proportional to the duration of illness. There was a tendency that the greater the degree of the anterior dural shift and compression of the spinal cord, the greater the severity of the disease. We thought that the anterior shift of the posterior lower cervical dura mater provides the clue to understanding of its etiology and methods of arresting the progression of the disease.     

Pathogenesis of juvenile muscular atrophy of unilateral upper extremity in reference to venous congestion of epidural space]

MRI and dynamic CT studies were performed in a young male with juvenile muscular atrophy of unilateral upper extremity (JM) with onset at age 15 and clinical course of 2 years. The mechanism of development of congestion in vertebral venous plexus was considered. Dynamic CT of the head in the neck flexion showed rapid reflux of blood from the intervertebral veins into the posterior internal vertebral venous plexus at the C5-C6 level and consequent congestion. It is speculated that in this patient some mechanism associated with head anteflexion led to a reflux into the valveless posterior internal vertebral venous plexus and congestion as well. Furthermore, it could be considered that anterior shift of the dural sac at the time of head anteflexion plays an important role in the development of this internal vertebral venous plexus congestion in JM.     

Symptomatological and electrophysiological study on cold paresis in juvenile muscular atrophy of distal upper extremity (Hirayama's disease)]

Patients with juvenile muscular atrophy of distal upper extremity (Hirayama's disease) often show marked weakness of the fingers occurring with exposure to cold. We term this phenomenon cold paresis. We conducted an original test to induce cold paresis (Cold Paresis Inducement Test) in 11 patients of this disease and 10 normal controls. Cold paresis was induced in 9 of 11 patients, but was not induced in the 2 patients who had the disease longer than 20 years and in all normal controls. We examined the electromyogram of abductor digiti minimi during 5 Hz and 20 Hz rate of ulnar nerve stimulation at cooling. The patients in whom cold paresis was induced exhibited a waning of amplitude of compound muscle action potential (M wave) during 20 Hz stimulation. This waning was aggravated by intravenous administration of anticholinesterase (edrohponium). We found a remarkable conduction delay of M waveform at the waning by means of waveform analysis. These results suggest that cold paresis may be caused by a conduction block of the muscle fiber membrane in re-innervating muscles after active denervation.     

Th2 shift in juvenile muscular atrophy of distal upper extremity: a combined allergological and flow cytometric analysis

Juvenile muscular atrophy of the distal upper extremity (JMADUE) is considered to be a type of flexion myelopathy; however, we recently reported cases of JMADUE associated with airway allergy successfully treated by plasma exchange. To further characterize the allergo-immunological features of JMADUE, 11 consecutive JMADUE patients in the neurology clinic at Kyushu University Hospital were studied. Past and present together with family histories of common allergic disorders were investigated. Total serum IgE was measured by an enzyme linked immunosorbent assay (ELISA) and allergen-specific IgE by a liquid phase enzyme immunoassay. Intracellular interferon (IFN) gamma-, interleukin (IL)-4-, IL-5- and IL-13-producing T cells in peripheral blood were analyzed by flow cytometry. Data from 42 healthy subjects were used as controls for allergological studies. Flow cytometric data from 21 healthy subjects were also used for comparison. The patients exhibited significantly higher frequencies of coexisting airway allergies such as allergic rhinitis (p=0.0057) and pollinosis (p=0.0064), family histories of allergic disorders (p=0.0075), and mite antigen specific IgE (p=0.0361) compared with the healthy subjects. Patients with JMADUE had a significantly higher percentage of IFNgamma-IL-4+CD4+T cells (p=0.0017), but not IL-5- or IL-13-producing CD4+T cells, and a reduced intracellular IFNgamma/IL-4 ratio in CD4+T cells (p=0.002) compared to the controls. These findings suggest that JMADUE has a significant T helper 2 (Th2) shift, which may in part contribute to the development of spinal cord damage.     

单肢肌萎缩/平山病:41例患者临床、电生理和颈椎MRI特征分析

目的 探讨单肢肌萎缩(MMA)/平山病患者的临床、肌电图及颈椎MRI特征。方法 2009年5月至2014年5月就诊本科,符合诊断标准的患者,连续登记并详细记录及分析人口学资料、临床、电生理和颈椎自然位和屈曲位MRI资料。结果(1)共41例,男39例、女2例,发病年龄14～24岁、平均年龄(16.87±2.62)岁。病程1～121月、平均病程(22.13±26.25)月。双上肢均有临床症状者6例(14.6%),症状局限单侧者35例(85.4%); 单侧者左12例(29.3%)、右23例(56.1%)。冷麻痹22例,指震颤9例,手麻木4例; 41例均有手固有肌萎缩,均无感觉障碍;(2)症状侧尺和正中神经运动潜伏期延长,小指展肌、拇短展肌运动波幅减低,小指展肌/拇短展肌波幅比值减小;(3)症状侧针肌电图显示异常自发活动者的出现率,在第一骨间肌和小指展肌为100%、拇短伸肌90.1%、拇短展肌86.3%、肱桡肌16.8%、肱二头肌13.8%; 在仅限于单侧症状的35例患者中,无症状侧手固有肌也显示异常自发活动者占51.4%;(4)32例患者完成颈椎MRI检查。自然位时32例均显示颈2-颈7椎体后方下缘连线与椎体相交; 均显示下段颈髓萎缩变扁平,其中位于C5-C7节段14例,C5-C6节段6例,C6-C7节段7例,C5-T1节段5例; 屈颈位时15例显示硬膜腔后壁前移,移位的硬膜后方可见硬膜外占位,内有流空信号,恢复自然位后占位消失。9例显示髓内可疑T₂异常高信号。结论 MMA/平山病主要见于青少年男性; 电生理表现为低位颈髓前角细胞病变,且无症状侧可显示临床下神经源性损害; 小指展肌/拇短展肌波幅比值减小,是有鉴别意义的电生理指标; 屈颈位颈椎MRI对于诊断很重要。结合临床、神经电生理及影像表现,有助于更全面认识本病。     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Indian patients

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder involving degeneration of anterior horn cells of spinal cord resulting in progressive muscle weakness and atrophy. AIMS: The molecular analysis of two marker genes for spinal muscular atrophy (SMA) i.e, the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP) was conducted in 39 Indian patients with clinical symptoms of SMA. Out of these, 28 showed homozygous deletions and the phenotypic features of these SMA patients were compared with the corresponding genotypes. SETTINGS: A tertiary care teaching Hospital. DESIGN: This is a prospective hospital based study. MATERIALS AND METHODS: Polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was used to detect the deletion of exon 7 and exon 8 of SMN1 gene, as well as multiplex PCR for exon 5 and 13 of NAIP gene. RESULTS: Exons 7 and 8 of SMN and NAIP (exon 5) were homozygously deleted in 73% of SMA I and 27% of SMA II patients. SMN exon 7 and 8 deletions without NAIP deletions were seen in 27% of type I SMA and 46% of SMA type II patients. Two patients of type III SMA showed single deletion of SMN exon 7 along with 27% of SMA type II patients. CONCLUSION: With the advent of molecular biology techniques, SMN gene deletion studies have become the first line of investigation for confirmation of a clinical diagnosis of SMA. The findings of homozygous deletions of exons 7 and/or 8 of SMN1 gene confirms the diagnosis of SMA, even in patients with atypical clinical features. Deletions of NAIP gene were mainly seen in severely affected patients, hence is useful for predicting the prognosis.     

A case of juvenile-type distal and segmental muscular atrophy of upper extremities (Hirayama disease) with the isolated cervical fusion at the C3-C4 levels

The case, 29-year-old male, had suffered from muscular weakness and atrophy of the bilateral forearms and hands with tremor of the bilateral fingers for about 13 years. A neurological examination showed normal muscle-stretch reflexes and no sensory disturbances. A cervical spinogram revealed a fusion at the C3-C4 levels and mild spondylotic changes. We clinically diagnosed him as juvenile-type distal and segmental muscular atrophy of upper extremities (Hirayama disease) with the isolated congenital cervical fusion. Magnetic resonance imaging demonstrated an enlargement of the anterior epidural space from the C4-C5 levels to the Th 1-Th 2 levels. This abnormal epidural space showed relatively high signal intensity partially with low signal intensity on the T2 weighted spin-echo image and decreased in signal on the T1 weighted spin-echo image. And the dural sac was shifted backward and narrowed. And the soft discs was slightly protruded at the level of C4-5, C5-6 and C6-7. These findings suggest the over swelling and the delayed blood flow of the internal vertebral venous plexus. In this case, the degeneration of the cervical spine and soft disc derived from the congenital cervical fusion seems to have caused the internal vertebral venous plexus congestion and then have damaged the anterior horn cells.     

肝豆状核变性患者脑MRI特征与临床表现的相关性研究

目的 探讨肝豆状核变性(wilson disease WD)患者头部MRI特征与临床表现的相关性.方法 对79例确诊WD患者的头部MRI特征与临床症状及其它主要辅助检查资料进行分析.结果 根据首次头部MRI检查结果,将患者分为A组(14例):头部MRl检查无异常发现;B组(65例):头部MRI检查有异常发现.病变集中于豆状核、脑干、尾状核和丘脑,多呈长T2W长T2W信号,但8例患者呈现短T2W其中2例为长T2W短T2W混杂信号.A、B两组年龄有显著性差异,A组患者神经系统检查全部正常,B组中有9例患者神经系统检查正常.WD患者脑部病变部位与病程之间无统计学意义(P＞0.05).构音障碍与尾状核关系较为密切,肌张力障碍与中脑的关系较为密切,震颤与丘脑的关系较为密切.结论 MRI检查是诊断WD的有效方法,头部MRI异常信号可先于临床表现而出现,病变较集中于豆状核、脑干、尾状核和丘脑,短T2W信号为本病具特征性的病理改变.WD患者脑部病变部位与病程之间无很好相关性,构音障碍与尾状核关系较为密切,肌张力障碍与中脑的关系较为密切,震颤与丘脑的关系较为密切.     

Correlation between sequential changes in angiographical findings and clinical deteriorations during management for dural AVM of the cavernous region]

The authors treated five patients with dural arteriovenous malformation of the cavernous region (DAVM) by cervical compression procedure as the initial treatment. In four of five patients clinical symptoms were aggravated during that period. The period between the beginning of cervical compression and the deterioration of clinical symptoms ranged from 11 to 20 days. In three of four patients, the angiography examined at the time of deteriorations confirmed the same amount of A-V shunt flow and otherwise the remarkable decrease of the draining pathway compared to the findings of the angiogram performed before the management. The angiography examined at the time of the remission of the symptoms showed the increase of the draining pathway in two patients and the resolution of the DAVM in another. These findings indicate that clinical courses of the DAVM and the amount of the draining pathway correlate to each other and that cervical compression procedure may occlude the important draining pathway of the DAVM.