Myasthenic Crisis and Concomitant Takotsubo Syndrome Complicated by Shock: A Case Report.

A man in his 80s with myasthenia gravis (MG) developed dysmobility and chest discomfort. An electrocardiogram revealed ST-segment elevation, and coronary angiography revealed Takotsubo syndrome (TTS). He experienced myasthenic crisis that required ventilation and shock that was refractory to vasopressors and required intra-aortic balloon pump (IABP) insertion. He was managed conservatively without MG-specific treatment until his hemodynamics improved. On hospital day 6, he was weaned from IABP. MG is a high-risk condition for TTS, and TTS with MC is associated with high mortality. We successfully managed this case of TTS with MC with intubation and IABP, without MG-specific treatment.

Iliopsoas Hematomas in a Patient with Progressive Encephalomyelitis with Rigidity and Myoclonus.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and severe syndrome characterized by rigidity of the limb and truncal muscles, brainstem signs, myoclonus, and hyperekplexia. Iliopsoas hematoma is a serious complication of bleeding disorders that occurs most commonly in patients with hemophilia and also in association with anti-coagulant drug treatment. We herein present a case of PERM complicated with bilateral iliopsoas hematomas. His neurological symptoms improved after immunotherapy, and thereafter the iliopsoas hematomas disappeared. Neurologists should consider iliopsoas hematomas as a serious potential complication of PERM.

Novel SPG11 Mutations in a Patient with Symptoms Mimicking Multiple Sclerosis.

We describe the cases of two sisters with spastic paraplegia 11 (SPG11). The younger sister developed relapsing lesions in the brain white matter with enhancement during the acute phase that mimicked multiple sclerosis (MS). The elevation of myelin basic protein in the cerebrospinal fluid (CSF) suggested demyelination, but a normal IgG index, the absence of oligoclonal bands, and the ineffectiveness of steroid treatment indicate that an autoimmune mechanism may not have been involved. In these affected sisters, we identified novel compound heterozygous mutations in the SPG11 gene. Our cases indicate the possible existence of a broader phenotypic spectrum of SPG11 mutations.

Acute Cerebellar Ataxia Induced by Nivolumab.

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.

Adult-onset Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke (MELAS)-like Encephalopathy Diagnosed Based on the Complete Sequencing of Mitochondrial DNA Extracted from Biopsied Muscle without any Myopathic Changes.

The clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are not uniform. We herein report a male patient with unusual MELAS-like encephalopathy who had been experiencing isolated recurrent stroke-like episodes since he was 33 years old without any particular family history. Despite an extensive investigation, he had no other signs suggestive of MELAS. Although the muscle pathology showed a normal appearance, a mitochondrial genome sequence analysis of the biopsied muscle revealed a heteroplasmic m.10158T>C mutation in the mitochondrial complex I subunit gene, MT-ND3. To prevented further deterioration of the higher brain function, the early diagnosis and treatment of mitochondrial stroke-like episodes is important.

[Familial progressive external opthalmoplegia, parkinsonism and polyneuropathy associated with POLG1 mutation].

Multiple mitochondrial DNA (mtDNA) deletions usually occur secondarily to a mutation in one of the enzymes involved in mtDNA maintenance, such as polymerase γ, which is encoded by the nuclear polymerase γ1 gene (POLG1) and POLG2. Patients with multiple mtDNA deletion disorders show clinical heterogeneity of symptoms, in addition to usually seen progressive external ophthalmoplegia (PEO). We conducted clinical, histological and genetic analyses of two affected sisters in a family with the autosomal dominant inheritance pattern of PEO. A 73-year-old woman (patient 1) with congenital hypogonadism and PEO developed L-dopa responsive parkinsonism about the age of 60. Neurological examination revealed mild proximal muscle weakness and polyneuropathy too. Her 69-year-old sister (patient 2) also showed PEO, parkinsonism and polyneuropathy. Histopathological studies of biopsied muscle specimens from patient 1 revealed numerous ragged red fibers as well as fibers with increased succinate dehydrogenase activity and decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected, both by Southern blot and long-range PCR assays of total DNA from the biopsied muscle specimens. A systemic mutational analysis in both sisters revealed a heterozygous p.Y955C (c.2864A>G) mutation in POLG1. This is the first Japanese family identified with this mutation. We reviewed cases with this mutation highlighting a wide phenotypic spectrum of this disorder.

Neuromelanin MRI in a family with mitochondrial parkinsonism harboring a Y955C mutation in POLG1.

BACKGROUND: Progressive external ophthalmoplegia (PEO) and parkinsonism can be caused by genetic mutations that affect mitochondrial DNA (mtDNA) maintenance. We characterized parkinsonism in a family with dominantly inherited PEO. METHODS: We conducted clinical, histological and genetic analyses on two affected members suffering from PEO and parkinsonism, and reviewed the cases in the literature. To clarify parkinsonism related to multiple mtDNA deletions, we used 3-T neuromelanin magnetic resonance imaging (MRI) to assess signal changes in the substantia nigra (SN) and locus ceruleus (LC) in our patients, and compared the results to those observed in idiopathic Parkinson's disease (iPD) (n = 35). RESULTS: We report the first case of a Japanese family harboring a heterozygous p.Y955C mutation in POLG1. The clinical features of parkinsonism related to the Y955C mutation in a total of 16 patients, including our two cases, are indistinguishable from iPD. However, neuromelanin MRI showed a distinct pattern in our cases compared to iPD. The neuromelanin imaging results were consistent with the neuropathological findings reported in cases of POLG1 mutations, in which neurons of the SN were profoundly affected while those in the LC were preserved. CONCLUSIONS: Our results suggest that 3-T neuromelanin MRI may be useful for differentiating POLG1 mutation-associated parkinsonism from iPD, and that POLG1 mutations may cause selective neuronal loss in the SN via a mechanism different from that of iPD.

Various S-GOT/S-GPT ratios in nonviral liver disorders and related physical conditions and life-style.

The relationship between the GOT/GPT ratio in nonviral liver disorders and underlying physical condition and life-style were evaluated. The subjects were 12,808 male railway company workers who underwent an annual health checkup. Nonviral liver disorders were defined as elevated transaminases (GOT > 76 IU/liter or GPT > 86 IU/liter, while negative for hepatitis B and C markers (282 cases). Controls were 9,783 males with normal findings for GOT, GPT, and y-GTP. By logistic regression analysis, GOT-dominant liver disorders were significantly related to alcohol consumption, hypertriglyceridemia, and diabetes mellitus. They were still significant on multivariate analysis. GPT-dominant liver disorders were significantly related to obesity, less exercise, hypercholesterolemia, and hypertriglyceridemia. Obesity and hypercholesterolemia were significant on multivariate analysis. In conclusion, the relationship between hypertriglyceridemia or diabetes mellitus and GOT-dominant disorders, which was not explained empirically, could indicate another pathogenesis for nonviral liver disorders, such as underlying insulin resistance.