Focal Amyotrophy Research Articles

An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary

Dr Khemani and colleagues have presented a diagnostically challenging case of a sporadic, adult onset ataxia (SAOA) syndrome resembling Multiple System Atrophy cerebellar type (MSA-C), with an atypical presentation of focal amyotrophy, eventually diagnosed as spinocerebellar ataxia type 3 (SCA3) [ [1] Khemani P. Elliott M. Levine T. An Atypical Clinical Course of a 71-Year-Old Man with Right Arm Weakness and Ataxia. Parkinsonism Relat Disord, 2022 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. The patient had presented elsewhere three years prior, with a Miller Fisher syndrome (MFS) associated with an elevated antiGQ1b antibody titer. However, as the patient had become wheelchair bound over the subsequent three years, the initial diagnosis of MFS is perhaps questionable. When evaluating ataxic disorders, it is important to establish the disease onset and course accurately. As the patient had a progressive cerebellar syndrome, the possible causes could be categorized broadly as: primary autoimmune (paraneoplastic or non-paraneoplastic); or neurodegenerative (sporadic or genetic). Primary autoimmune cerebellar ataxia encompassing paraneoplastic ataxia syndromes, and immune-mediated ataxias (gluten ataxia and anti-GAD65 ataxia) may present insidiously, with accumulating disability especially if timely and appropriate immunosuppressive therapies are not instituted [ [2] Hadjivassiliou M. Graus F. Honnorat J. Jarius S. Titulaer M. Manto M. Hoggard N. Sarrigiannis P. Mitoma H. Diagnostic criteria for primary autoimmune cerebellar ataxia-guidelines from an international task force on immune-mediated cerebellar ataxias. Cerebellum. 2020; 19: 605-610 Crossref PubMed Scopus (35) Google Scholar ].

Clinical Scales Used in Motor Neuron Disease

Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

Hirayama disease: An ayurvedic approach

Introduction: Hirayama disease, also known as Monomelic amyotrophy or benign focal amyotrophy, is a rare motor neuron disease. It is reported to primarily affect males of southeast Asia, particularly India and Japan. Clinical findings and Intervention: A 27 years male patient approached Ayurveda OPD with a known case of Hirayama Disease from last 9 years. Considering this condition, the treatment was planned according to Ayurvedic Medicinal system which included courses of Nasya karma, Basti karma and Shamana aushadi. Outcome: Post treatment, the patient showed considerable clinical improvement, and arrest in disease progression was observed. Conclusion: The present condition is understood under the spectrum of Vata vyadhi and was diagnosed as a case of Viswachi. The treatment was focused upon pacifying vata Dosha and restoring strength and functional capacity.

Clinical, electrophysiological and MRI profile of Hirayama disease: A case series

Introduction: Hirayama disease (HD) is focal amyotrophy in young adults, and commonly involves distal upper limbs, often misdiagnosed as motor neuron disease and writer’s cramp. This often leads to delay in the diagnosis and results in disease progression. In this study, we have analyzed clinical, radiological and electrophysiological profile of patients presenting with hand wasting and weakness. Materials and Methods: Patients presenting with insidious onset of hand wasting (January 2014 to February 2017) were evaluated clinically and electro physiologically. Cervical MRI in neutral and flexion position was done. Results: All 16 patients were male, were less than 25 years of age, with median age of 22 years. Duration of illness was 3 months to 7 years. All patients presented with insidious onset of progressive weakness and lower motor neuron type of wasting of hands. Nine (56.25%) patients presented with right sided, five (31.25%) with left sided and another two (12.5%) presented with bilateral asymmetric weakness and wasting. None of the patients had neck pain or radicular symptoms. Twelve (75%) had cold paresis, eight (50%) had minipolymyoclonus and five (31.25%) had fasciculations. Electromyography (EMG) showed chronic denervation in the C7T1 myotomes. In MRI, localized lower cervical cord atrophy was seen in 13 (81.25%) cases. Asymmetric cord flattening was noted in 14 (87.5%) cases. Loss of dural attachment in 13 (81.25%), anterior displacement of dorsal dura on flexion in 14 (87.5%) and epidural flow voids were seen in 14 (87.5%) cases. Enhancing epidural crescent in flexion was seen in all 12/16 (75.0%) cases. Intramedullary hyper intensity was seen in 2 (12.5%) patients. Conclusions: 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 differentiate it from other progressive conditions and to institute early therapy.

The Importance of Flexion MRI in Hirayama Disease with Special Reference to Laminodural Space Measurements

Hirayama disease is a benign focal amyotrophy of the distal upper limbs involving C7, C8, and T1 segmental myotomes with sparing of the brachioradialis and proximal muscles of the upper limb innervated by C5-6 myotomes. The objective of the present study was to study the utility of MR imaging in young patients presenting with weakness and wasting of the distal upper extremity and to evaluate the importance of the laminodural space during flexion cervical MR imaging. This was a prospective cross-sectional study conducted from January 2014 to July 2017 in a tertiary care center from Northeast India. Forty-five patients with clinically definite Hirayama disease underwent electrophysiologic evaluation followed by MR imaging of the cervical spine. The mean age at recruitment was 22.8 ± 5.5 years. Forty patients (88.9%) had unilateral and 5 (11.1%) had bilateral upper extremity involvement. Cervical cord T2-weighted hyperintensities were demonstrated in 16 patients (35.6%), of which 15 (33.3%) had anterior horn cell hyperintensities. Flexion MR imaging showed loss of the posterior dural attachment, forward shifting of the posterior dural sac with postcontrast enhancement, and prominent posterior epidural venous plexus in all patients. The laminodural space at maximum forward shifting of the posterior dural sac ranged from 3 to 9.8 mm, with a mean distance of 5.99 mm (95% confidence interval, 5.42-6.57 mm). Flexion cervical MR imaging is a very useful investigation in diagnosing Hirayama disease. The increase in the laminodural space and the presence of cervical cord flattening during flexion are essential for diagnosis.

Intraneural Perineurioma of Unilateral Radial and Median Nerves Manifesting With Long-Standing Focal Amyotrophy in a 14-Year-Old-Boy

Intraneural perineuriomas are rare tumors of the peripheral nerves with unique immunohistochemical findings. In this report, we highlight the clinical and imaging findings of an adolescent male with histologically proven intraneural perineurioma involving multiple nerves. The salient features included a clinically progressive course, imaging evidence of involvement of long segments of multiple nerves, enlargement of individual fascicles within the affected nerves, and intense contrast enhancement of the enlarged fascicles. The identification of enlarged fascicles with intense contrast enhancement within the affected and distended nerve segments may aid in distinguishing intraneural perineurioma from other tumors affecting the peripheral nerves.

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.

Familial Asymmetric Distal Upper Limb Amyotrophy (Hirayama Disease)

Hirayama disease is a rare nonprogressive, predominantly unilateral, juvenile distal upper limb amyotrophy that involves C7, C8, and Th1 innervated muscles. The etiology and pathogenesis of this focal amyotrophy is presently unknown. There is a debate as to whether Hirayama disease is an unusual neck flexion induced cervical myelopathy or an intrinsic motor neuron disease. Despite being a sporadic disorder, familial forms have been occasionally described, with either autosomal recessive or dominant inheritance. We describe a 3-generation Greek family, with 4 members affected by a benign distal upper limb amyotrophy of long duration, reminiscent of Hirayama disease, suggesting an autosomal dominant inheritance pattern. Hypothesizing that this familial amyotrophy might be related to autosomal dominant distal spinal muscular atrophy type V(dSMA-V) that is characterized by prominent involvement of the distal upper extremities, we tested the index case for glycyl tRNA synthetase and Berardinelli-Seip congenital lipodystrophy (BSCL2) N88S and S90L gene mutations (by direct sequencing) that are involved in the development of dSMA-V phenotype. Despite the phenotypical similarity of this familial amyotrophy to dSMA-V, no missense mutation in the genes presently associated with it was detected. The reported family is the first in the literature with occurrence of Hirayama amyotrophy in 3 generations of a family. Considering that familial forms of Hirayama amyotrophy are uncommon, it could be assumed that they might represent a different subtype of the same disease having the same clinical features but different pathogenesis.

Atopic myelitis with focal amyotrophy: A possible link to Hopkins syndrome

Among 22 consecutive patients with myelitis, of unknown etiology, and atopic diathesis (atopic myelitis) who from April 2002 to March 2006 had been studied in our clinic, 5 (23%) showed focal amyotrophy in one or two limbs. These 5 patients were subjected to combined clinical, electrophysiological, neuroimaging and immunological studies. Ages were 18 to 58-years-old (average 39). Four showed amyotrophy of unilateral or bilateral upper limbs while one showed amyotrophy in both thighs. All patients showed on-going denervation potentials in the affected muscles, while motor conduction study including F wave was normal except for in one patient who showed prolonged F wave latency in one nerve. Two had localized high signal intensity lesions involving anterior horns on spinal cord MRI and three showed abnormalities suggesting pyramidal tract involvement on motor evoked potentials. All had a present and/or past history of atopic disorders and specific IgE against common environmental allergens, such as mite antigens and cedar pollens, and four showed mild eosinophilia, all of which were compatible with atopic myelitis. When clinical and laboratory findings were compared between atopic myelitis with (n=5) or without focal amyotrophy (n=17), the former showed a significantly higher frequency of present and past history of asthma (80% vs. 24%, p=0.0393) and tended to have higher EDSS scores (3.8+/-1.6 vs. 3.1+/-1.4). Two patients showed mild to moderate improvements after immunotherapies such as methylprednisolone pulse therapy or plasma exchange, while two recovered with low dose corticosteroids and one without treatment had a gradually progressive course. Although atopic myelitis preferentially involves the posterior column of the cervical spinal cord, it is possible that anterior horn cells are affected in some cases of atopic myelitis, especially in patients with asthma. This suggests a possible link between atopic myelitis and Hopkins syndrome (asthmatic amyotrophy).

Muscle infarction in a young woman with brittle type 1 diabetes

We present the first case of muscle infarction in a 30-year-old woman who had a 5-year history of type 1 diabetes mellitus that was not complicated by nephropathy, retinopathy or neuropathy. All common causes of muscle infarction were excluded, particularly microangiopathy and a hypercoagulable state. The differential diagnosis included infection (pyomyositis, necrotic fasciitis), focal inflammatory myositis, vascular events, trauma, tumor and diabetic amyotrophy, all of which were excluded. In spite of good glycaemic control, her diabetes remained brittle; alternating states of transient acute hypoglycaemia and hyperglycaemia may have been responsible for the infarction. Brittleness resumed after treatment with subcutaneous insulin infusion using a portable pump. No recurrence of muscle infarction was observed during a 18-month follow-up.

Focal Amyotrophy In Neurofibromatosis 2

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by bilateral vestibular schwannomas and other CNS tumours including meningiomas and spinal schwannomas. Occasionally, peripheral neuropathy occurs in these patients but this is the first report of focal amyotrophy. Clinical, electrophysiological, and imaging data from four NF2 patients seen at a specialist neurofibromatosis clinic over a 4 year period are described in whom symptomatic focal amyotrophy preceded the diagnosis of NF2. Two presented with wasting and weakness of a single muscle group, several years before NF2 was diagnosed. In one patient a mononeuritis multiplex was the presenting feature of NF2, and in one patient focal wasting and weakness developed after the diagnosis of NF2 was made. In none of the four cases could a focal peripheral nerve or root neurofibroma be identified despite extensive imaging with MRI, and the limitations of neuroimaging for identifying a structural cause in patients with NF2 with a focal peripheral nerve lesion is discussed. It is likely that NF2 may affect peripheral nerve structures in a manner distinct from a compressive schwannoma.

Selective paraspinal muscle amyotrophy

A 56-year-old female presented with mild low back pain. Examination revealed severe, selective atrophy of the thoracic and lumbar paraspinal muscles. Fibrillations were seen in the paraspinal muscles on EMG. Limb EMG was normal. Biopsy of the gluteus maximus was normal. Paraspinal muscle biopsy revealed neurogenic features. Atrophy of the thoracic and lumbar paraspinal muscles was noted on magnetic resonance imaging. This patient has selective amyotrophy of the thoracic and lumbar paraspinal muscles. This may be an addition to the spectrum of ‘benign focal amyotrophy’. The differential diagnosis of paraspinal muscle weakness is discussed.

MRI findings in Hirayama's disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama's disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama's disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4-C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama's disease is an intrinsic motor neuron disease.

5-02-06 Benign focal amyotrophy: Neuroradiological, genetical, immunological and electromyographic study of three cases

5-02-06 Benign focal amyotrophy: Neuroradiological, genetical, immunological and electromyographic study of three cases

The impact of the approval of riluzole.

The approval of riluzole as the first agent to treat ALS has raised a number of important questions and brought the treatment of ALS into a new era. In addition to patients with classic ALS in whom a modest improvement in life expectancy was shown compared with placebo, what other patients might benefit from riluzole? Should patients with progressive muscular atrophy (PMA) be given the drug? Benign focal amyotrophy? At-risk patients with familial disease in whom the SOD1 gene defect has been identified? What about healthy patients from families with autosomal dominant ALS without identifiable gene defects? Because each treatment trial has used different outcome measures, when insulin-like growth factor-I (IGF-I) or the next agent is approved, how will we decide which agent or agents to use? Recognizing that no data currently exist to …

PS. Delayed visual reaction time of patients with unilateral spatial neglect syndrome — analysis under different stimulation sites and different tasks

A 56-year-old female presented with mild low back pain. Examination revealed severe, selective atrophy of the thoracic and lumbar paraspinal muscles. Fibrillations were seen in the paraspinal muscles on EMG. Limb EMG was normal. Biopsy of the gluteus maximus was normal. Paraspinal muscle biopsy revealed neurogenic features. Atrophy of the thoracic and lumbar paraspinal muscles was noted on magnetic resonance imaging. This patient has selective amyotrophy of the thoracic and lumbar paraspinal muscles. This may be an addition to the spectrum of ‘benign focal amyotrophy’. The differential diagnosis of paraspinal muscle weakness is discussed.

A CASE OF ACUTE BRONCHIOLECTASIS

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by bilateral vestibular schwannomas and other CNS tumours including meningiomas and spinal schwannomas. Occasionally, peripheral neuropathy occurs in these patients but this is the first report of focal amyotrophy. Clinical, electrophysiological, and imaging data from four NF2 patients seen at a specialist neurofibromatosis clinic over a 4 year period are described in whom symptomatic focal amyotrophy preceded the diagnosis of NF2. Two presented with wasting and weakness of a single muscle group, several years before NF2 was diagnosed. In one patient a mononeuritis multiplex was the presenting feature of NF2, and in one patient focal wasting and weakness developed after the diagnosis of NF2 was made. In none of the four cases could a focal peripheral nerve or root neurofibroma be identified despite extensive imaging with MRI, and the limitations of neuroimaging for identifying a structural cause in patients with NF2 with a focal peripheral nerve lesion is discussed. It is likely that NF2 may affect peripheral nerve structures in a manner distinct from a compressive schwannoma.