[Tuberculous Meningitis in Which Inflammation Cannot Be Adequately Suppressed by Standard Therapy: How to Think and Treat].

Tuberculous meningitis is the most severe form of tuberculosis and often causes critical illness with high mortality. Treatment should be initiated without waiting for a definitive diagnosis of tuberculous meningitis. Although we often experience treatment-resistant tuberculous meningitis, it is important to continue examination and treatment.

[A case of severe acute flaccid myelitis requiring continuous mechanical ventilation].

Many cases of acute flaccid paralysis occurred during an enterovirus D68 (EV-D68) outbreak in North America in the fall of 2014, and this epidemic has been newly defined as a distinct disease entity named acute flaccid myelitis (AFM). This disease entity is relatively popular among pediatricians, whereas it remains little-known among neurologists in Japan. We reported a 7-year-old girl with AFM, in whom severe limb weakness and respiratory failure developed five days after appearance of respiratory symptoms. Clinical features of our case were mimicked by those of acute axonal motor neuropathy at early stage of the disease, and this resulted in delayed diagnosis of AFM. DNA of EV-D68 was not detected. There are few reported cases of severe AFM, in which artificial ventilation is needed for a long time including both acute and recovery phases of the illness, and functional prognosis of AFM is discussed by literature.

Antecedent infections in Fisher syndrome: sources of variation in clinical characteristics.

The clinical features of Guillain-Barré syndrome (GBS) are highly variable, according to the type of antecedent infection. Although a major GBS phenotype, Fisher syndrome (FS), has been shown to be preceded by infections similar to those preceding GBS, whether or not the clinical features in FS also vary according to antecedent infection remains unclarified. Frequent antecedent infections among this study of 70 FS patients included Haemophilus influenzae [n = 15 (21%)], Campylobacter jejuni [n = 10 (14%)], and cytomegalovirus (CMV) [n = 6 (8.6%)]. Compared with other FS patients, H. influenzae-seropositive FS patients more frequently had a history of prior upper respiratory tract infection; double vision as the initial symptom; and, except for oculomotor disturbance, more rarely showed cranial nerve involvement. C. jejuni-related FS occurred predominantly in younger male patients and characteristically presented with blurred vision. According to GBS disability scale, CMV-related FS tended to be more severe, although every patient received immunotherapy. Serum anti-GQ1b IgG antibodies were detected in most cases, regardless of antecedent infection type. At the nadir of illness, the most frequent diagnosis in H. influenzae-related cases was "pure FS" without limb weakness or central nervous system involvement (71%), in C. jejuni-related cases "incomplete FS" such as acute ophthalmoparesis with or without ataxia (60%), and in CMV-related cases (50%) advanced conditions such as GBS overlap and Bickerstaff brainstem encephalitis. These findings indicate that the type of preceding infection determined the neurological features of FS. CMV-related FS appeared to be similar to H. influenzae- and C. jejuni-related FS regarding anti-GQ1b antibody-mediated pathogenesis, as opposed to CMV-related GBS.

Distal limb weakness phenotype of Guillain-Barré syndrome.

OBJECTIVE: Several regional variants of Guillain-Barré syndrome (GBS) have been proposed in western countries, but other variants remain unclear, especially among mildly disabled cases. The aim of this study was to identify unvalidated GBS phenotypes among Japanese patients with mild GBS. METHODS: Retrospective study of a cohort of patients at a University Hospital in Japan. RESULTS: Among 107 GBS patients, 25 (23%) were classified as having mild GBS (GBS disability scale ≤ 2 at nadir). A review of mild cases identified 8 patients (7.5% of all GBS and 32% of mild GBS) with an unusual phenotype, namely a distal limb weakness form of GBS (DL-GBS), which showed limited distribution of limb weakness within hands and feet with preserved strength in proximal limb muscles. The patients with DL-GBS were characterized by mild-to-moderate weakness in distal parts of limbs especially fingers, lacking or mild sensory disturbance at distal limbs, sometimes hyperreflexia at legs, and having prior Campylobacter jejuni enteritis. Among the patients with GBS after C. jejuni enteritis, DL-GBS patients were characterized by frequent detection of anti-GM1 antibodies without anti-GD1a antibodies, whereas the others were often positive for the two antibodies. CONCLUSIONS: DL-GBS is a distinct regional phenotype of GBS, which should be differentiated from cervical myelopathy. It can be generally categorized as a mild type of GBS after C. jejuni enteritis, which has characteristic pattern of anti-ganglioside autoantibodies.

Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease.

OBJECTIVES: To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations. DESIGN: Retrospective clinical and genetic review. SETTING: University hospital. PATIENTS: We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries. RESULTS: We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations. CONCLUSIONS: Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.

[Case of thrombotic thrombocytopenic purpura associated with clopidogrel].

We reported a Japanese first case of thrombotic thrombocytopenic purpura (TTP) induced by clopidogrel, a newly developed antithrombotic drug, marketed in May 2006 in Japan. This 80 years old woman developed cerebral infarction and suffered from Broca's aphasia and right hemiparesis. Clopidogrel was started on Day 6 after the onset. On Day 10, four days after the administration of clopidogrel, two egg-sized purpura with marked decrease in platelet count was found. The purpura extended over the entire body in next few days. Despite total seven times of plasma exchange, platelet count did not normalize. Twenty four days after the onset of TTP, the patient developed central catheter infection and died of sepsis. TTP will become a lethal side effect of clopidogrel, when diagnosis and treatment are late. Because it is assumed that the mechanism of clopidogrel induced TTP differs from that of ticlopidine, we should establish firm treatment urgently.