Background: Invasive and/or non-invasive mechanical ventilation are most important options of respiratory management in amyotrophic lateral sclerosis. Methods: We evaluated the frequency, clinical characteristics, decision-making factors about ventilation and survival analysis of 190 people with amyotrophic lateral sclerosis patients from 1990 until 2013. Results: Thirty-one percentage of patients underwent tracheostomy invasive ventilation with the rate increasing more than the past 20 years. The ratio of tracheostomy invasive ventilation in patients >65 years old was significantly increased after 2000 (25%) as compared to before (10%). After 2010, the standard use of non-invasive ventilation showed a tendency to reduce the frequency of tracheostomy invasive ventilation. Mechanical ventilation prolonged median survival (75 months in tracheostomy invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32 months). The life-extending effects by tracheostomy invasive ventilation were longer in younger patients ≤65 years old at the time of ventilation support than in older patients. Presence of partners and care at home were associated with better survival. Following factors related to the decision to perform tracheostomy invasive ventilation: patients ≤65 years old: greater use of non-invasive ventilation: presence of a spouse: faster tracheostomy: higher progression rate; and preserved motor functions. No patients who underwent tracheostomy invasive ventilation died from a decision to withdraw mechanical ventilation. Conclusion: The present study provides factors related to decision-making process and survival after tracheostomy and help clinicians and family members to expand the knowledge about ventilation.

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We report the case of a 25-year-old man with multiple sclerosis (MS) who had severe headache and unconsciousness. He suffered from optic neuritis that had started at age 6. From the age of 12 years, he had suffered from multiple sclerosis (MS) cerebral lesions that relapsed three times over for 5 years. At age 25, he showed a new lesion in the cerebellar cortex, suggesting an exacerbation of the MS. However, magnetic resonance imaging findings the next day showed cerebral venous sinus thrombosis. His laboratory findings showed low antithrombin activity. Genetic analysis revealed a single-base substitution (C>T) at the codon 359 (Arg to STOP) in the 5th exon portion of the antithrombin gene, heterozygote. In the literature review, 17 cases of multiple sclerosis associated with cerebral venous sinus thrombosis, which occurred after the lumbar puncture and the treatment with high-dose methylpredonisolone in 11 of these cases. In our case, antithrombin deficiency, hyperhomocystinemia, infection, and lumbar puncture were suggested as the risk factors.

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We report a case of human immunodeficiency virus (HIV) infection that showed subacute progressive cerebellar ataxia without HIV encephalopathy or other encephalopathies, including progressive multifocal leukoencephalopathy or encephalitis of other human herpes virus (HHV) infections. A 43-year-old man exhibited unsteady gait. Neurological examination disclosed ataxia of the trunk and lower extremities. Personality change and dementia were absent. Magnetic resonance imaging did not reveal any abnormal finding, including of the cerebellum. The serum HIV-1-RNA was 1.2 × 10⁵ copies/ml, and the absolute CD4 lymphocyte count was 141 cells/ml. Remarkably, the serum anti-Yo antibody, as an anti-cerebellar antibody of paraneoplastic syndrome, and anti-gliadin antibody, associated with celiac disease or gluten ataxia, were positive. The cerebrospinal fluid (CSF) immunoglobulin G index was 1.2 (< 0.8), and oligoclonal bands were present. PCR of the CSF was negative for HIV, JC virus, other HHVs, and mycosis. Previous reports presented HIV-infected patients with concurrent autoimmune diseases such as systemic lupus erythematosus, anti-phospholipid syndrome, autoimmune thrombocytopenia, vasculitis, polymyositis and dermatomyositis, sarcoidosis, Graves’ disease, and hepatic diseases. These might have been present in patients with a CD4 T lymphocyte count of more than 200 cells/ml. On the other hand, paraneoplastic syndrome, gluten ataxia, cerebellar ataxia associated with anti-glutamic acid decarboxylase antibody, and Hashimoto’s encephalopathy might manifest as autoimmune cerebellar ataxia. As regards the association of HIV infection and autoimmune cerebellar ataxia, a previous report suggested that anti-gliadin antibody was detected in about 30% of HIV-infected children, though there is no reference to an association with cerebellar ataxia. Moreover, to our knowledge, detection of anti-Yo antibody in an HIV-infected patient with cerebellar ataxia has not been reported. These findings suggest that, although it is extremely rare, clinicians need to consider HIV infection in a patient exhibiting autoimmune cerebellar ataxia.

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Here, we report two cases of episodic ataxia type 2 (EA2) in a 63-year-old woman and her 36-year-old daughter. The mother experienced recurrent attacks of cerebellar dysfunction lasting 4 to 5 hours since the age of 41 years. On several occasions, she was admitted to the emergency room, where she was diagnosed with epilepsy or stroke. Based on these diagnoses, she was treated with antiepileptic or anticoagulant drugs, but both treatments were eventually discontinued. The frequency of the attacks increased after the patient reached the age of 62. Interictal neurological examination demonstrated signs of slight cerebellar ataxia, i.e. saccadic eye movements, gaze-directed nystagmus, and mild truncal ataxia. Brain magnetic resonance imaging (MRI) showed cerebellar vermis atrophy. Electroencephalography (EEG) revealed various spike and wave patterns: solitary spikes, spike-and-slow wave complexes, and slow wave bursts. Photoparoxysmal response (PPR) type 3 was also observed. Treatment with acetazolamide abolished the patient’s attacks almost completely. The daughter started experiencing 5- to 10-minute ataxic episodes at the age of 16 years. Based on her epileptiform EEG activities with PPR (type 2), antiepileptic drugs (valproate and zonisamide) were prescribed. Despite pharmacological treatment, the attacks recurred; however, their frequency gradually decreased with time, until they almost entirely disappeared when the patient was 33. Unfortunately, migraine-like headaches arose instead. Subtle truncal ataxia was observed during interictal periods. Sanger sequencing of the exons of the CACNA1A gene revealed a novel single base deletion (c.3575delA) in both patients. Despite the difference in age of onset and clinical course, both patients showed clearly epileptiform EEG activities without experiencing the concurrent epileptic episodes. Thus, EA2 is a disease that may be misdiagnosed as epilepsy or stroke in the field of emergency medicine.

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A previously healthy 16-year-old girl developed sudden eye pain and visual loss in her right eye. On day 7 from onset her right visual acuity had decreased to light perception, and she underwent 5 courses of intravenous methylprednisolone therapy (IVMP, 1 g/day for 3 consecutive days per week). Her eye pain and her visual acuity had improved immediately. Eleven months later, follow-up MRI revealed three T₂-hyperintense plaques involving subcortical white matter in the left occipital lobe, right frontal lobe, right thalamus, and thoracic spinal cord. We suspected the diagnosis as multiple sclerosis and treated with fingolimod. She developed recurrent optic neuritis (ON) on day 19 from fingolimod therapy, and we stopped fingolimod. For two years from onset she was admitted five times due to recurrences of ON and appearance of white matter lesion and myelitis. At 22 months, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies revealed to be positive in her sera from the onset to the present. Our case report suggests that fingolimod might not be effective in anti-MOG antibody-related disorders together with anti-aquaporin-4 (AQP4) antibody-positive group.

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Fingolimod, a sphingosine-1-phosphate receptor modulator, inhibits the egress of CCR7-positive lymphocytes, including encephalitogenic lymphocytes, from lymph nodes and may sometimes cause lymphopenia. A recent study reported that varicella zoster virus reactivation occurred in the saliva of 20% of multiple sclerosis (MS) patients treated with fingolimod. I compared the risk of developing herpes zoster between 32 MS patients treated with fingolimod (FTY-MS) and 45 patients, including those with neuromyelitis optica spectrum disorder, horizontal hemianopsia without anti-aquaporin-4 antibodies, and myelitis with anti-myelin oligodendrocyte glycoprotein antibodies, treated with tacrolimus (TCR-NMO). The risk of developing herpes zoster in FTY-MS (40/1,000 patient-years) was significantly higher than that in TCR-NMO (6/1,000 patient-years) (P < 0.0001, odds ratio: 6.90). The incidence of herpes zoster of patients with rheumatoid arthritis treated with Tofacitinib in Asian countries has been shown to be higher than those of patients in the United States or European countries. It may be better to pay more attention to develop herpes zoster in Japanese MS patients treated with fingolimod.

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A 70-year-old woman who have achieved complete remission (CR) of acute promyelocytic leukemia (APL) with all-trans retinoic acid and chemotherapy presented with abnormal sensation in the right lateral thigh and the bilateral legs. In addition, neurological examination revealed weakness of the left shoulder abduction, the right hand, and the bilateral lower limbs. Atypical promyelocytes were detected in the cerebrospinal fluid, in spite of normal finding in the peripheral blood smear. Magnetic resonance imaging showed gadolinium-enhanced multiple intradural/extramedullary lesions in the whole spine. Nerve conduction studies of the right limbs revealed sensorimotor conduction abnormalities, conspicuously in the posterior tibial and sural nerves. As a result, she was diagnosed as having intrathecal relapse of APL, associated with multiple mononeuropathy. The neurological symptoms were completely disappeared by intrathecal chemotherapy and whole-spine radiotherapy, suggesting that the neuropathy was possibly caused by meningeal infiltration affecting multiple spinal nerve roots. Since extramedullary or intrathecal relapse is extremely rare in APL compared with other types of leukemia, precise neurological evaluations and suitable treatment should be performed immediately, when APL patients with CR manifest some neurological symptoms.

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Proximal dominant muscle weakness is rare in transthyretin (TTR)-related familial amyloid polyneuropathy (FAP). A 69-year-old Japanese man developed numbness and dysesthesia of the first, second and third digits of both hands since 2008. He presented to our hospital with one year history of progressive proximal muscle weakness in the lower extremities since 2013. Neurological examinations revealed predominant proximal muscle weakness and atrophy with areflexia in the lower extremities, decreased superficial sensation in the first, second and third fingers of both hands, and decreased superficial and deep sensation in the lower extremities. Nerve conduction studies revealed an axonal degeneration type of sensorimotor polyneuropathy and bilateral carpal tunnel syndrome. Electromyogram revealed acute and chronic neurogenic changes predominantly in proximal muscles. We performed biopsy of the left quadriceps muscle and observed neurogenic changes in the muscle tissue and an amyloid deposition in the adipose tissue. This amyloid deposition was not seen in endomysium, perimysium and blood vessels. Genetic analysis of the TTR gene revealed the patient was heterozygous for a single nucleotide substitution c.379 A>G, which resulted in the replacement of valine with isoleucine at position 107 of the mature protein. We diagnosed his condition as FAP with Amyloid Transthyretin (ATTR) Ile107Val.

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A 75-year-old man was admitted to our hospital because of repeated transient visual obscurations of greying vision. The transient visual obscurations were caused by rotating his neck or the Valsalva manoeuver, and they recovered in about 30 seconds. A few weeks later, pulsatile tinnitus of the right ear and a dull headache developed. Both ocular fundi showed papilledema, and there was significant intracranial hypertension on cerebrospinal fluid examination. He was diagnosed as having right sigmoid sinus thrombosis and a dural arteriovenous fistula with a rapid arteriovenous shunt from the right ascending pharyngeal artery and the right occipital artery to the right transverse sinus. Anticoagulant therapy was started, and coil embolization was performed. The transient visual obscurations, headache, and tinnitus improved dramatically after the procedure. We hypothesized that the transient visual obscurations were triggered by rotating the neck or performing the Valsalva manoeuver as they both increase the pressure of cerebrospinal fluid, inducing transient optic nerve ischemia and visual obscurations under mild intracranial hypertension. Transient visual obscurations are an important initial symptom of intracranial hypertension.

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[in Japanese]

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