Evaluation of the applicability of weak shoulder and arm sparing signs in amyotrophic lateral sclerosis by multiple neurologists and neurology residents: A single-center study.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) exhibits selective muscle weakness. The weak shoulder and arm sparing signs, assessed by a single experienced neurologist, have been reported to be superior to previous signs in sensitivity and specificity. However, it is unknown whether the same results are observed when assessed by multiple neurologists. METHODS: Subjects were retrospectively identified from our department's inpatient database from 2014 to 2023. Medical Research Council (MRC) scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles were evaluated. The weak shoulder sign was defined as positive when Del was weaker than BB and TB. The arm sparing sign was defined as positive when both Del and FDI were weaker than BB and TB. Sensitivity was analyzed in all ALS patients and in subgroups based on the region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and the Japanese ALS Severity Classification. RESULTS: Seventy-one patients with ALS were identified. Eight neurologists and three neurology residents evaluated each patient's MRC scores. The weak shoulder and arm sparing signs were observed in 72% and 48% of patients, respectively, with no significant difference in sensitivity across patient subgroups. DISCUSSION: The weak shoulder and arm sparing signs showed high and moderate sensitivity, respectively, consistent with a previous report, even when evaluated by multiple examiners. This expands the clinical utility and increases the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments.

Mimic of transient ischemic attack by anemia-induced asterixis: A novel differential diagnosis of stroke with critical pitfalls.

As most cases of asterixis with metabolic causes are asymptomatic, they have not been considered in the differential diagnosis of stroke. However, an asterixis occasionally resembles a transient ischemic attack (TIA). On the other hand, reports have indicated that anemia is an independent risk factor for brain ischemia. Therefore, both asterixis and anemia are important considerations for stroke diagnosis. A 79-year-old man with frequent leg palsy was initially diagnosed with recurrent TIA at the anterior cerebral artery (ACA) with a tiny callosal infarction and aspirin was prescribed immediately. However, subsequent careful physical examination revealed asterixis at both the wrist and knee joints. Laboratory testing and colonoscopy revealed severe anemia secondary to colon cancer. Blood transfusion immediately improved the asterixis and gait, thus confirming that anemia contributed to the patient's symptoms. This novel etiology of asterixis may be accompanied by misleading anemia-induced brain ischemic lesions detectable on magnetic resonance imaging (MRI). Anemia-induced asterixis should be considered as a novel differential diagnosis of a stroke to avoid pitfalls leading to unnecessary stroke treatment for patients with anemia.

Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments.

BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. METHODS: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489). RESULTS: The median (interquartile range) age at onset of neurological symptoms was 69 (64.2-70) years in the ATTRv amyloidosis vs 12 (5-37.2) years in CMT group (Mann-Whitney U, p < 0.01). The proportion of patients with initial sensory symptoms was 70% in the ATTRv amyloidosis group vs 7.1% in CMT group (Fisher's exact, p < 0.01). The proportion of patients with histories of suspected chronic inflammatory demyelinating polyneuropathy (CIDP) were 50% in the ATTRv amyloidosis group vs 8.7% in CMT group (Fisher's exact, p < .01). Other measures and outcomes were not different between the two groups. Five of the six patients with ATTRv amyloidosis received treatment and survived. INTERPRETATION: For effective treatments, the transthyretin gene should be screened in patients with suspected CMT with old age at onset of neurological symptoms, initial sensory symptoms, and histories of suspected CIDP.

Tic Movement of Thyroid Cartilage as a Cause for Localized Cerebral Embolism: Mimics of Embolic Stroke of Undetermined Source with Non-Stenotic Carotid Plaque.

Several studies have suggested that non-stenotic carotid plaque was a risk factor for embolic stroke of undetermined source in some patients. However, individual backgrounds of these patients is unclear. We encountered a 64-years-old female with cerebral emboli, from an apparently stable non-stenotic carotid plaque (only 1.42mm thick) at the distal left common carotid artery, caused by violent tic movement of thyroid cartilage under well controlled dyslipidemia. Even though the plaque appeared thin and stable, mechanical stimulation could cause multiple, unnaturally localized emboli by stimulation-induced atherogenesis and plaque rupture, resulting in a misdiagnose of embolic stroke of undetermined source with non-stenotic carotid plaque.

Diagnostic uncertainty of steroid-modified Marburg's variant of multiple sclerosis even at autopsy: A case suggesting lymphoma and related myelin loss.

MS (multiple sclerosis) has specific criteria to avoid misdiagnosis. However, the Marburg variant of MS is so fulminant that initial axonal damage and other atypical observations have been allowed in past reports. We present a 74-year-old autopsy case with a vanishing tumor after steroids and radiation therapy, which was pathologically diagnosed as a Marburg variant with initial axonal loss. The case displayed radiological lymphoma-like observations: mass effects protruding to the lateral ventricle, fused extension from the choroid plexus to white matter with C opening sign, a growing lesion from the skull dura mater, high in diffusion-weighted imaging and low in apparent diffusion coefficient on magnetic resonance imaging (MRI) suggesting high cell density lymphoma. In addition, clinical manifestations were atypical for MS: upper limb monoplegia without ipsilateral lower limb involvement, pleocytosis over 50 cells/µL, and class 3 cytological abnormality in cerebrospinal fluid. However, at autopsy following steroids and radiation therapy, there were no lymphoma-like lesions, such as mass effects, fused extensive lesions, masses on the skull dura mater, or high cell density lesions. Instead, there were only myelin losses corresponding to the MRI lesions, highlighting the potential for contamination by other diseases in steroid-modified Marburg's variant of multiple sclerosis, possibly due to lymphoma, even at autopsy.

Case Report: Anti-mGluR5 antibody-negative Ophelia syndrome with failed lymph node biopsy due to steroid therapy.

Ophelia syndrome is paraneoplastic limbic encephalitis (PLE) with Hodgkin lymphoma. Some Ophelia syndrome patients have been reported as testing positive for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies. However, we experienced a case of anti-mGluR5 antibody-negative Ophelia syndrome. The type of onset, neurological symptoms, and imaging as well as electroencephalographic findings were like previous reports except for a normal cell count in cerebrospinal fluid (CSF). Unfortunately, a lymph node biopsy failed and could not diagnose the patient before death because steroid treatment for limbic encephalitis had shrunk lymph nodes. We believe it is essential to accumulate cases of this syndrome and clarify the association between PLE and Hodgkin lymphoma so chemotherapy can be initiated even if malignant lymphoma cannot be pathologically proven or when antibodies cannot be measured or are negative.

Distressing Belching with Chorea Induced by Caudate Infarction.

Although belching is mostly associated with gastrointestinal disorders, it occasionally accompanies movement disorders such as Parkinsonism or dystonia. A woman in her 80s presented distressing belching and chorea of the right arm and leg from 3 years earlier. A brain MRI showed a left caudate infarction and atrophic change. Haloperidol significantly improved belching and chorea. Caudate infarction can cause distressing belching with chorea. It might be important to select the appropriate drug by referring to the accompanying involuntary movement to treat belching with movement disorders.

Focal brain lactate accumulation in metformin-induced encephalopathy without systemic lactic acidosis: A case report suggesting mitochondrial vulnerability in lentiform fork sign.

Metformin causes metabolic encephalopathy in some patients with end-stage chronic kidney disease, resulting in impaired consciousness and parkinsonism. This encephalopathy has a very characteristic magnetic resonance imaging feature in lentiform nuclei known as the "lentiform fork sign". However, the mechanism is unknown. Here, we report a case of metformin-induced encephalopathy with a novel observation of lactate accumulation in the lentiform nuclei on magnetic resonance spectroscopy without systemic lactic acidosis. Since metformin is an inhibitor of mitochondrial complex-I, this focal brain lactate accumulation implies that a part of the pathogenesis of metformin-induced encephalopathy is the focal vulnerability of mitochondria to metformin in the lentiform nuclei. When metformin causes encephalopathy, not only testing for serum lactic acidosis and performing routine magnetic resonance imaging but also evaluation of brain lactate accumulation by magnetic resonance spectroscopy should be required to elucidate the etiology.

Hidden relationship between fingolimod and bleeding: Possible novel management of fingolimod-associated lymphopenia.

Fingolimod, a functional antagonist of sphingosine-1 phosphate receptor, is a disease modifying drug of multiple sclerosis and its remarkable adverse effect is peripheral lymphopenia because the drug retains lymphocyte in the secondary lymphoid tissues. Therefore, in theory, when severe bleedings occurred, the fingolimod-treated patients could not compensate for the loss of lymphocytes induced by bleedings because of the retention in the secondary lymphoid tissues. In addition, because most of the fingolimod is reported to be distributed in the erythrocytes, and the erythrocytes are the main regulator of serum sphingosine-1 phosphate concentration, bleeding may also affect metabolism of fingolimod and prognosis of multiple sclerosis. However, no study had focused the relationship between fingolimod and bleedings in multiple sclerosis. We encountered the first case in which fingolimod-associated lymphopenia worsened synchronously with gynecological bleeding, and was improved by the bleeding prophylaxis, uterine myomectomy. This case had statistically significant positive correlation between the serum hemoglobin level and peripheral lymphocyte count (P = 0.0000000507). We then had three similar cases. In these 4 correlative patients out of the 14 fingolimod-treated patients in our institution, the importance of the bleeding in fingolimod-treated patients was indicated by line graphs, point diagrams, and statistically significant correlation coefficients. Bleeding should be focused on by all of physicians treating multiple sclerosis with fingolimod.

Guillain-Barré Syndrome and Posterior Reversible Encephalopathy Syndrome following Spinal Surgery.

Guillain-Barré syndrome (GBS) typically occurs after gastroenteritis and respiratory tract infection, but surgery has also been considered one of the triggers. Posterior reversible encephalopathy syndrome (PRES) is a rare complication of GBS. A normotensive female in her 70s presented ascending paralysis and frontal-parieto-occipital subcortical lesions with intermittent hypertension after spinal surgery. Nerve conduction studies revealed demyelinating polyneuropathy. The patient's brain lesions disappeared with amelioration of hypertension. She was diagnosed with the demyelinating form of GBS and PRES caused by intermittent hypertension. Intravenous immunoglobulin G (IVIG) improved her symptoms without exacerbation of the PRES. Surgery can be a trigger of GBS, and GBS can cause PRES by hypertension and present as central nervous lesions. It is important to treat hypertension before using IVIG when PRES is suspected as a complication of GBS, since the encephalopathy can be exacerbated by IVIG. There may be more undiagnosed cases of the coexistence of GBS and PRES after surgery because surgery itself can also cause PRES. Proper control of blood pressure and confirmation of negative central nervous lesions are required to treat GBS patients with IVIG safely.

Parkinsonism Improved With Levodopa After Endoscopic Third Ventriculostomy in Shunted Hydrocephalus Due to Aqueductal Stenosis.

INTRODUCTION: Levodopa-responsive parkinsonism has been reported following ventriculoperitoneal (VP) shunt in patients with obstructive hydrocephalus due to aqueductal stenosis. It has been thought to arise from injury to the global rostral midbrain including the nigrostriatal pathway by a transtentorial pressure gradient. We present a similar patient, but his parkinsonism resisted levodopa administration during the initial therapy. CASE REPORT: A 51-year-old man suffered from hydrocephalus due to secondary aqueductal stenosis presumably attributed to massive bleeding during surgery for a fourth ventricle hemangioblastoma. After resolution of the hydrocephalus with VP shunt, he developed severe parkinsonism, Parinaud syndrome, and hyperreflexia, suggesting global rostral midbrain dysfunction, but high-dosage levodopa therapy was not effective. An inverted transtentorial pressure gradient suggested by his unilateral slit-like ventricle was assumed to be the cause of the levodopa resistance. Also based on an assumption that the absorption of cerebrospinal fluid was impaired due to the intraoperative bleeding, a lumbar peritoneal shunt was added to the preexisting VP shunt, but it failed to control the ventricular size. Instead, endoscopic third ventriculostomy stabilized it, characteristically inducing levodopa responsiveness in our patient. An increase of the levodopa dosage led to clinical improvement, which needed a maintenance dosage because of dependency. CONCLUSION: The details of this patient suggest that a transtentorial pressure gradient may have impaired more distal basal ganglia connections over a global rostral midbrain including the nigrostriatal pathway, and that aggressive levodopa therapy after endoscopic third ventriculostomy can be effective for refractory parkinsonism.