Brachial Amyotrophic Diplegia Research Articles

Clinical and serological insights into paraneoplastic brachial amyotrophic diplegia.

Brachial amyotrophic diplegia (BAD) is typically linked to a neurodegenerative etiology such as amyotrophic lateral sclerosis (ALS). Clinical and serological characterizations of paraneoplastic neurologic syndromes resembling BAD are limited. A retrospective chart review of patients with BAD-like presentations was conducted. Clinical/paraclinical features of paraneoplastic BAD and neurodegenerative BAD cases were compared. Between 2017 and 2023, 13 cases of BAD were identified, of these 10 were neurodegenerative BAD (ALS variant), and 3 cases associated with paraneoplastic autoimmunity. An additional paraneoplastic BAD case diagnosed in 2005 was included. LUZP4-IgG was detected in all four paraneoplastic cases, with coexisting KLHL11-IgG in three cases and ANNA1 (anti-Hu)-IgG in one case. Out of the four paraneoplastic cases, two patients had seminoma, while the remaining two had limited cancer investigation. Three patients exhibited bi-brachial weakness as the initial symptom before the onset of brainstem symptoms or seizures. Compared to BAD patients with a neurodegenerative etiology, a higher proportion of paraneoplastic cases had ataxia (75% vs 0%, p = 0.011). Other clinical features only detected in the paraneoplastic BAD group were vertigo (n = 2), hearing loss (n = 2) and ophthalmoplegia (n = 2). Electrodiagnostic studies in these patients revealed cervical myotome involvement, supportive of motor neuronopathy. All paraneoplastic cases but none of the neurodegenerative BAD cases exhibited inflammatory cerebrospinal fluid (CSF) findings (lymphocytic pleocytosis and/or supernumerary oligoclonal bands; p = 0.067). Despite the administration of immunotherapy and/or cancer treatment, none of the paraneoplastic patients reported clinical improvement. BAD or bi-brachial neurogenic weakness is a rare phenotypic presentation associated with paraneoplastic autoimmunity. Co-existing features of brainstem dysfunction or cerebellar ataxia should prompt further paraneoplastic evaluation. Common serological and cancer associations among these cases include LUZP4-IgG and KLHL11-IgG, along with testicular germ cell tumors, respectively.

Asymmetrical Onset of Leg Amyotrophic Diplegia (LAD): A Case Report

Progressive muscular atrophy (PMA) comprises approximately 10% of patients with motor neuron disease (MND). Some of the patients presenting initially as PMA will develop when followed over time upper motor neuron findings leading to the diagnosis of ALS. True PMA cases represent a pure lower motor neuron presentation of sporadic motor neuron disease and are in a spectrum with ALS and PLS. While PMA typically affects both the arms and legs, some patients have predominantly upper extremity involvement and others may have selective leg weakness referred to respectively as brachial amyotrophic diplegia (BAD) 1,2 and leg amyotrophic diplegia (LAD).3 These cases of progressive muscle atrophy remain restricted to a body region for extended periods. These are considered slow regional variants of motor neuron disease. LAD is a leg onset variant of progressive muscular atrophy (PMA). LAD weakness is confined to the legs for at least 2 years, and there are no upper motor neuron signs.4A LMN syndrome confined to legs LAD was first described by Pierre Marie and his student Patrikios in 1918 and was known as the pseudopolyneuritic variant of ALS, the Marie-Patrikios form, or the peroneal form of ALS.Here is another case of LAD for the neuromuscular literature.

The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease

Disruption in copper homeostasis causes a number of cognitive and motor deficits. Wilson's disease and Menkes disease are neurodevelopmental disorders resulting from mutations in the copper transporters ATP7A and ATP7B, with ATP7A mutations also causing occipital horn syndrome, and distal motor neuropathy. A 65 year old male presenting with brachial amyotrophic diplegia and diagnosed with amyotrophic lateral sclerosis (ALS) was found to harbor a p.Met1311Val (M1311V) substitution variant in ATP7A. ALS is a fatal neurodegenerative disease associated with progressive muscle weakness, synaptic deficits and degeneration of upper and lower motor neurons. To investigate the potential contribution of the ATP7AM1311V variant to neurodegeneration, we obtained and characterized both patient-derived fibroblasts and patient-derived induced pluripotent stem cells differentiated into motor neurons (iPSC-MNs), and compared them to control cell lines. We found reduced localization of ATP7AM1311V to the trans-Golgi network (TGN) at basal copper levels in patient-derived fibroblasts and iPSC-MNs. In addition, redistribution of ATP7AM1311V out of the TGN in response to increased extracellular copper was defective in patient fibroblasts. This manifested in enhanced intracellular copper accumulation and reduced survival of ATP7AM1311V fibroblasts. iPSC-MNs harboring the ATP7AM1311V variant showed decreased dendritic complexity, aberrant spontaneous firing, and decreased survival. Finally, expression of the ATP7AM1311V variant in Drosophila motor neurons resulted in motor deficits. Apilimod, a drug that targets vesicular transport and recently shown to enhance survival of C9orf72-ALS/FTD iPSC-MNs, also increased survival of ATP7AM1311V iPSC-MNs and reduced motor deficits in Drosophila expressing ATP7AM1311V. Taken together, these observations suggest that ATP7AM1311V negatively impacts its role as a copper transporter and impairs several aspects of motor neuron function and morphology.

14. Autoimmune lower motor neurone disorder – Case report

Motor neurone diseases (MND) traditionally include a broad spectrum of neuromuscular disorders. First, we have to mention sporadic forms of ALS (amyotrophic lateral sclerosis) with mixed clinical presentation (syndromes with upper and lower motor neurone signs), then the isolated central type (primary lateral sclerosis, PLS) and at last the isolated peripheral type (primary muscular atrophy, PMA). The existence of familiar hereditary and genetic MND forms is well known, e.g. superoxide dismutase (SOD-1) and dynactin gene mutations are known to cause PMA variants also called LMND (lower motor neurone disease). Selected LMND cases are associated to specific autoantibodies. For example an asymmetric lower motor neurone syndrome with predominant distal involvement is associated to IgM anti-GM1 or to IgM anti-GalNAc-GD1a. Another LMND variant is an asymmetric lower motor neurone syndrome with particular damage of proximal upper extremities muscles (also known as Vulpian–Bernhard syndrome, brachial amyotrophic diplegia or flail arm syndrome) can be associated in 10–20% cases to anti-asialo GM1 autoantibodies. We present a patient’s case report with suspected Vulpian–Bernhard syndrome with bilateral non-symmetric cervico-brachial amyotrophy without sensory impairment. The autoimmune aetiology was clearly proven by clinical responsiveness to immunosuppression/immunomodulation therapy mainly to repetitive intravenous human polyclonal immunoglobulin application (IVIG).

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants.

Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL-ALS than other variants, but a considerable proportion of UL-ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL-ALS. Conversely, an absent ADM CMAP was identified only in UL-PMA and BAD. The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS.

Adult Sandhoff Disease With 2 Mutations in the HEXB Gene Presenting as Brachial Amyotrophic Diplegia

Sandhoff disease is a rare autosomal recessive metabolic disorder of GM2 gangliosides. It is caused by a lack of functional N-acetyl-β-D-glucosaminidase A and B because of mutations in the HEXB gene. We describe a 55-year-old woman with adult Sandhoff disease presenting as brachial amyotrophic diplegia. The assay of total hexosaminidase involving A and B showed decreased level of these activities. Hex-A was 4.6 nmol·min·mL (normal: 7.0-20.0 nmol·min·mL) and Hex-B was 0.1 nmol·min·mL (normal: 1.0-10.0 nmol·min·mL), respectively. Analysis of HEXB gene demonstrated 2 point mutations that were located at the exon 5 (c.619A>G) and exon 11 (c.1250C>T). Compound heterozygosity of these 2 mutations may trigger the development of distinct adult Sandhoff disease phenotype. Sandhoff disease should be considered in the differential diagnosis of lower motor neuron disease, such as brachial amyotrophic diplegia, even if the age at onset is more than 50 years.

Brachial amyotrophic diplegia associated with a novel SOD1 mutation

Background: Brachial amyotrophic diplegia (BAD) is an adult-onset subtype of lower motor neuron disease mainly affecting men, largely restricted to proximal arm and shoulder girdle muscles without involvement of lower limbs or appearance of pyramidal signs. BAD is considered a sporadic disorder although a SOD1 mutation (L106P) was recently described in a patient with BAD.

Leg Amyotrophic Diplegia

To identify the frequency of leg amyotrophic diplegia (LAD) at a US academic center, describe the pattern of weakness, and provide comparative data from 8 additional major US academic institutions. LAD is a leg onset variant of progressive muscular atrophy (PMA). LAD weakness is confined to the legs for at least 2 years, and there are no upper motor neuron signs. We present a retrospective chart review of 24 patients with the LAD presentation from the University of Kansas Medical Center ( n = 8 cases) and from 8 US academic institutions (n = 16 cases). Of the 318 subjects identified in the University of Kansas Medical Center Neuromuscular Research Database, 82% (260 subjects) had amyotrophic lateral sclerosis (ALS), 1.9% (6) had familial ALS, 6.6% (21) had primary lateral sclerosis, and 9.2% (29) had lower motor neuron (LMN) disease. Of these 29 cases, 16 had PMA, 5 had brachial amyotrophic diplegia, while 8 had LAD. The mean LAD age of onset was 58 years with a male/female ratio of 3/1. Onset was asymmetric in 7/8. We identified a pelviperoneal pattern of weakness (sparing of knee extension and/or ankle plantar flexion) in 4 cases and distal predominant weakness in 3 cases. All patients had electrodiagnostic findings consistent with motor neuron disease confined to the lower extremities. We present LAD disease duration and survival data from 8 major academic neuromuscular centers. At last follow-up, weakness progressed to involve the arms in 6/24 LAD cases and of these 6 cases, 2 patients died from progression to typical ALS. From onset of symptoms, mean survival in LAD is 87 months, with 92% of cases being alive. The natural history of LAD differs from typical forms of ALS and PMA. LAD is a slowly progressive disorder that accounts for a fourth of LMN disease cases. An asymmetric pelviperoneal pattern of weakness should heighten the suspicion for LAD.

Brachial amyotrophic diplegia associated with the a140a superoxide dismutase 1 mutation

Brachial amyotrophic diplegia associated with the a140a superoxide dismutase 1 mutation

102. A 62-year-old man with brachial amyotrophic diplegia in the setting of complete human immunodeficiency virus viral load suppression for many years

102. A 62-year-old man with brachial amyotrophic diplegia in the setting of complete human immunodeficiency virus viral load suppression for many years

Follow Up of Brachial Amyotrophic Diplegia - Report of Two Cases -

Follow Up of Brachial Amyotrophic Diplegia - Report of Two Cases -

Diaphragmatic involvement without bulbar dysfunction or features to suggest amyotrophic lateral sclerosis in brachial amyotrophic diplegia

Diaphragmatic involvement without bulbar dysfunction or features to suggest amyotrophic lateral sclerosis in brachial amyotrophic diplegia

Natural history and clinical features of the flail arm and flail leg ALS variants

We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome [FA]) and the pseudopolyneuritic variant (flail leg syndrome [FL]) of amyotrophic lateral sclerosis (ALS; motor neuron disease). We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan- Meier method and Cox proportional hazards model. In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p < 0.001) and 69 months for FL syndrome (p < 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p < 0.001), and FL syndrome 71 months (p = 0.001). The flail arm (FA) and flail leg (FL) syndromes had significantly better survival than typical amyotrophic lateral sclerosis (ALS) or progressive muscular atrophy cases that were not classified as FA or FL. Our findings underline the clinical and prognostic importance of the FA and FL variants of ALS.

Man-in-the-barrel syndrome, a symmetrical proximal brachial amyotrophic diplegia related to motor neuron diseases: a survey of nine cases

To report on 9 patients presenting with sporadic motor neuron disease , who over a long period of time evolved with a symmetrical proximal brachial amyotrophic diplegia. Nine patients were followed-up who , displayed, since onset, a progressive limitation of arm flexion/abduction resulting in a peculiar posture with both hands hanging loosely beside the trunk. Electrophysiological test results were consistent with lower motor neuron disease. Cervical MRI was performed in all patients. Nine male subjects with ages ranging from 38 to 73 years at onset of symptoms, developed bilateral and symmetric paresis and atrophy of upper limb muscles. Proximal muscles were more involved than the distal groups. In most patients tendon reflexes were absent or hypoactive in the upper limbs. Needle electromyography (EMG) revealed positive sharp waves and fibrillations and high amplitude polyphasic potentials with an incomplete recruitment pattern in most upper limb muscles. EMG of lower limb muscles was normal in some cases while abnormal in others. MRC did not disclose cervical spinal cord abnormalities from C5-T1. Attention is called to the Man-in-the-Barrel syndrome in some motor neuron diseases, especially in patients with progressive spinal atrophy and amyotrophic lateral sclerosis.

Brachial amyotrophic diplegia (segmental proximal spinal muscular atrophy) associated with HIV infection

Several forms of motor neuron disease occurring in association with HIV infection have been described. Segmental proximal spinal muscular atrophy or brachial amyotrophic diplegia, a rare segmental variant of motor...

G.P.11.01 Slow disease progression and prolonged survival in a patient with sporadic amyotrophic lateral sclerosis (ALS): A 28-year follow-up

To analyse the disease progression along 28years in one patient with ALS evolving from the brachial amyotrophic diplegia (BAD) to a clinical form fulfilling the El Escorial criteria for definite ALS. A 47-year-old man (no affected relatives, left clavicular fracture at 17years of age) presented with a 28-year history of progressive painless hands, arms and shoulder girdle weakness and later on pyramidal signs in lower extremities and bulbar signs. Weakness in the left hand began at 19years of age.

Brachial Amyotrophic Diplegia in a Patient With Human Immunodeficiency Virus Infection

Although amyotrophic lateral sclerosis and progressive spinal muscular atrophy have been recognized to occur in association with human immunodeficiency virus infection, to our knowledge, brachial amyotrophic diplegia, a form of segmental motor neuron disease, has not been previously reported. Brachial amyotrophic diplegia results in severe lower motor neuron weakness and atrophy of the upper extremities in the absence of bulbar or lower extremity involvement, pyramidal features, bowel and bladder incontinence, and sensory loss. We describe a human immunodeficiency virus-seropositive man without severe immunosuppression or prior AIDS-defining illnesses who had brachial amyotrophic diplegia. This disorder may represent one end of a spectrum of motor neuron diseases occurring with this retrovirus infection.

Brachial amyotrophic diplegia associated with a novel SOD1 mutation (L106P)

Brachial amyotrophic diplegia (BAD) is a subtype of sporadic lower motor neuron disease (LMND) presenting with adult onset, mainly in men, and remaining largely restricted to proximal arm and shoulder girdle muscles without involvement of the lower limbs or appearance of pyramidal signs.1,2 Mutations in the copper/zinc superoxide dismutase ( SOD1 ) gene have been described in familial cases of ALS and occurring in sporadic cases of ALS,3–4 but not in patients with BAD. We describe here a patient with BAD syndrome associated with a novel SOD1 mutation. A 77-year-old man was referred to our clinic for a 12-month history of bilateral painless arm weakness and wasting. The patient did not have a history of diabetes. Weakness began in the left arm and progressed to the proximal right arm 2 months later. Family history was unremarkable for neuromuscular disorders and entrapment neuropathies. There were no symptoms in the lower limbs or sphincter disturbances. Neurologic examination showed a peculiar posture of the “man in the barrel” with both hands hanging loosely at his …

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 60

Brachial amyotrophic diplegia (BAD) is defined the isolated upper limb weakness attributed to neurogenic atrophy, sparing lower extremity, respiratory and bulbar muscles. Although such phenotypes may be seen in number of conditions, previous reports pointed out that the label of BAD should refer to any patient with slowly and nonprogressive neurogenic atrophy of upper limbs remaining stable at least 18 months after initial presentation 50 year old man with unremarkable past history noticed after minor cervical spine trauma progressive weakness and wasting of left shoulder and arm which was followed within few months by gradual involvement of contralateral in relatively symmetric pattern. There were no symptoms in lower limbs, neck, bulbar muscles nor sphincter disturbances. On examination, patient exhibited a peculiar posture of both hands hanging loosely at his sides. There were fasciculations and atrophy of upper limb muscles. Reflexes could not be elicited in upper extremities but they were normal in the lower. Cranial nerves and sensory examination were unremarkable. Routine blood tests and search for GM1 antibodies were negative, whereas CK was found mildly elevated ( 361 mU/ml). Test for HIV‐1 was positive with RNA level of 144.920 copies/ml and CD4 count 403/mm3. Electrophysiology showed in both sides low amplitude of compound muscle action potentials, mildly reduced velocity without evidence of conduction block or of temporal dispersion. Sensory conduction study was normal. On EMG, there was loss of motor units, acute and chronic neurogenic changes. Cervical MRI was normal. Patient neurological disability did not show progression. The case reported exhibits the following notable aspects: clinical and electrophysiological abnormalities fully restricted to upper limbs, lack of significant demyelinating features as well as of GM1 antibodies, absence of clinical signs related to immunosuppression due to HIV‐1 infection.