Yuto Uchida

Combination of ketogenic diet and stiripentol for super-refractory status epilepticus: A case report

Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues for at least 24 h after initiation of general anaesthetic medications, including cases in which SE recurs on reduction or withdrawal of anaesthesia [1]. Given the severity of SRSE, there is a critical need for new therapies to halt ongoing seizure activity. Because neuronal excitation is regulated by energy metabolism, SRSE can be suppressed by inhibiting metabolic pathways. A ketogenic diet (KD) has been proven to be effective in critically ill adults with SRSE [2]; however, the mechanisms by which KD prevents seizures remain unknown. It has recently been found that one of the mechanisms that KD works on is a metabolic pathway via lactate dehydrogenase (LDH) and that LDH may be inhibited by stiripentol (STP) [3]. Here, we report that a combination of KD and STP appeared to constitute effective treatment of a patient with SRSE underlying anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. A 20-year-old Japanese woman presented with a week of headaches followed by impaired consciousness. On admission, she exhibited abnormal behaviours, including altered manner of speaking and shouting loudly. She was unable to follow commands and became unresponsive to external stimuli. An electroencephalogram (EEG) showed generalized rhythmic delta frequency activity at 1 Hz with superimposed, frontally predominant bursts of rhythmic beta frequency activity (extreme delta brushes) (Fig. 1(A-1)). Her cerebrospinal fluid demonstrated mild pleocytosis (74 cells per mm) with a slightly elevated IgG index (1.01). Glucose and protein concentrations were normal. She was diagnosed as having NMDAR encephalitis (positive anti-NMDAR antibody result) with bilateral ovarian teratomas (pelvic CT findings) (Fig. 1(B)). Her symptoms were not alleviated by bilateral ovariectomy and immunotherapy (plasma exchange, intravenous immunoglobulin at 400 mg/kg over 5 days and intravenous methylprednisolone at 1000 mg over 3 days). Additionally, her seizures were unresponsive to conventional antiepileptic drugs (AEDs) such as valproate, carbamazepine, phenytoin, clonazepam, phenobarbital, and levetiracetam. Further, these treatments repeatedly resulted in a generalized rash accompanied by fever, leukopenia, and acute hepatitis and they were accordingly ceased.

A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes

Non-dystrophic myotonias are caused by mutations of either the skeletal muscle chloride (CLCN1) or sodium channel (SCN4A) gene. They exhibit several distinct phenotypes, including myotonia congenita, paramyotonia congenita and sodium channel myotonia, and a genotype-phenotype correlation has been established. However, there are atypical cases that do not fit with the standard classification. We report a case of 27-year-old male who had non-dystrophic myotonia with periodic paralysis and two heterozygous mutations, E950K in CLCN1 and F1290L in SCN4A. His mother, who exhibited myotonia without paralytic attack, only harbored E950K, and no mutations were identified in his asymptomatic father. Therefore, the E950K mutation was presumed to be pathogenic, although it was reported as an extremely rare genetic variant. The proband experienced paralytic attacks that lasted for weeks and were less likely to be caused by CLCN1 mutation alone. Functional analysis of the F1290L mutant channel heterologously expressed in cultured cells revealed enhanced activation inducing membrane hyperexcitability. We therefore propose that the two mutations had additive effects on membrane excitability that resulted in more prominent myotonia in the proband. Our case stresses the value of performing genetic analysis of both CLCN1 and SCN4A genes for myotonic patients with an atypical phenotype.

Two brothers homozygous for the TTR V30M both presenting with a phenotype dominated by central nervous complications

Department of Neurology, Toyokawa City Hospital, 23 Noji, Yawata-cho, Toyokawa 442-8561, Aichi, Japan, Department of Neurology, Kumamoto University, Kumamoto, Japan, Department of Radiology, Toyokawa City Hospital, Aichi, Japan, Department of Neurology, Nagoya University, Aichi, Japan, Department of Neurosurgery, Toyokawa City Hospital, Aichi, Japan, and Department of Neurology, Nagoya City University, Aichi, Japan

Stiripentol for the treatment of super‐refractory status epilepticus with cross‐sensitivity

Cross‐sensitivity of rash has been reported between various antiepileptic drugs (AEDs). However, few studies have determined the frequency and management of cross‐sensitivity in patients with super‐refractory status epilepticus (SRSE).

ステロイド治療が有効であったサイトメガロウィルス感染後の急性運動・感覚・自律神経ニューロパチーの1例

We report a rare case of autonomic neuropathy associated with cytomegalovirus (CMV) infection. The patient, a 53-year-old male, was admitted to our hospital because of prolonged fever, headache and neck stiffness followed by urinary retention. Cerebrospinal fluid examination revealed pleocytosis (219/mm(3), predominantly lymphocytes) with a markedly increased protein level (217 mg/dl) and serum IgM anti-CMV antibody was detected. While his meningitic symptoms gradually improved after intravenous administration of ganciclovir, he complained of numbness in the extremities and difficulty in walking. Neurologically, marked orthostatic hypotension, glove and stocking type of paresthesia, severe muscle weakness in extremities, and neurogenic atonic bladder were noted. Nerve conduction studies showed normal except for F-waves, which were absent in the left tibial nerve. A sural nerve specimen appeared normal in both myelinated and unmyelinated fibers. He was given immunological therapies such as corticosteroid and intravenous high dose immunoglobulin therapies. After corticosteroid therapies, not only sensory and motor symptoms but also autonomic symptoms remarkably improved. Of the anti-ganglioside antibodies, IgM anti-GM1 antibody and IgM anti-GM2 antibody were detected. Although some cases with Guillain-Barré syndrome preceded by CMV infection have been reported, few cases with autonomic neuropathy have been described in association with successful corticosteroid therapies.

Failure to improve after ovarian resection could be a marker of recurrent ovarian teratoma in anti-NMDAR encephalitis: a case report

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis that can be paraneoplastic and usually responds to tumor resection and immunotherapy. More than 75% of patients with anti-NMDAR encephalitis fully recover or have only mild sequelae, whereas the remainder experience severe disability. It remains unknown why certain cases have refractory clinical disease courses. We report a case of anti-NMDAR encephalitis with bilateral ovarian teratomas who was refractory to tumor resection and early initiation of immunotherapy. During intensive care, immunohistochemical analyses of her cerebrospinal fluid showed persistently high reactivity of NMDAR antibody over time. Six months after the operation, pelvic computed tomography detected a recurrent ovarian teratoma. After total enucleation of the bilateral ovaries, with significant pathological findings of bilateral mature cystic teratomas, her clinical condition improved rapidly, paralleled by a decrease in anti-NMDAR reactivity. This case illustrates the need to keep considering why extensive treatment fails to influence the disease when we encounter patients with refractory anti-NMDAR encephalitis. Failure to improve after ovarian resection could be a marker of recurrent ovarian teratoma in anti-NMDAR encephalitis.

Miller Fisher Syndrome Mimicking Tolosa-Hunt Syndrome

We herein report a patient with Miller Fisher syndrome mimicking Tolosa-Hunt syndrome. A 47-year-old man presented with right orbital pain and diplopia. On a neurological examination, he had right oculomotor nerve palsy and diminished deep tendon reflexes. Brain magnetic resonance imaging failed to show any parenchymal lesions; however, the bilateral oculomotor nerves were gadolinium-enhanced. The presence of a triad of orbital pain, ipsilateral oculomotor nerve palsy, and a rapid response to steroid therapy met the diagnostic criteria for Tolosa-Hunt syndrome. After discharge, antibodies against GQ1b and GT1a were reported to be positive only with phosphatidic acid. The present case was ultimately diagnosed as an incomplete phenotype of Miller Fisher syndrome.

Fatal remote cerebral hemorrhage at a site of a microbleed immediately after intravenous thrombolysis

We report a patient with ischemic stroke who was treated with intravenous alteplase and subsequently developed a fatal pontine hemorrhage during cerebral angiography. An 88‐year‐old woman presented with right hemiplegia and aphasia. Magnetic resonance angiography at onset showed occlusion of the left middle cerebral artery. T2*‐weighted magnetic resonance imaging showed a cerebral microbleed in the pons. She was treated with intravenous alteplase followed by cerebral angiography. Left carotid angiography showed recanalization of the left middle cerebral artery, and neurointervention was not carried out. During the angiography, she became comatose. Computed tomography showed a massive pontine hemorrhage. The hemorrhage was considered to be attributable to the microbleed. The variety of time phases of cerebral microbleeds have been elucidated; there are a subset of lesions reflecting acute or subacute microhemorrhages. It is considered that expansion of a pontine microbleed induced by alteplase caused a fatal remote cerebral hemorrhage in the present case.

Opalski syndrome caused by vertebral artery dissection

A 52-year-old man developed sudden occipital headache followed by vomiting and vertigo. On admission, he displayed right Horner syndrome with ipsilateral reduced facial sensation to pain and temperature that crossed in the body, affecting the left limbs. In addition, he had right hemiparesis. Diffusion weighted magnetic resonance images showed a high intensity lesion localized in the lower and right lateral medulla oblongata. Magnetic resonance angiography showed severe luminal stenosis in the right vertebral artery and T2-weighted sampling perfection with application optimized contrasts using different flip angle evolution (SPACE) showed arterial wall expansion. T1-weighted SPACE showed subacute intramural hematoma at that point, suggesting arterial dissection. First described in 1946, Opalski syndrome is considered a variant of Wallenberg syndrome with ipsilateral hemiparesis. This motor impairment is considered as a result of extension of the ischemia from the lateral medulla to the upper cervical cord involving corticospinal fibers caudal to pyramidal decussation. This case adds information regarding the anatomy of the pyramidal decussation.