Paraneoplastic Opsoclonus-myoclonus Syndrome with Anti-Hu and Anti-SOX-1 Antibodies after Immune-checkpoint Inhibitor Treatment Combined with Chemotherapy in a Patient with Small-cell Lung Cancer.

A 69-year-old man with advanced small-cell lung cancer achieved partial remission after 3 courses of immunochemotherapy that included atezolizumab. Ten days after the last treatment, he developed paraneoplastic opsoclonus-myoclonus syndrome and required mechanical ventilation. Serology testing detected anti-Hu and anti-SOX-1 antibodies. Despite steroid pulse therapy, various anticonvulsants, continuous intravenous sedation, and a fourth course of chemotherapy without atezolizumab, his condition failed to improve. Paraneoplastic opsoclonus-myoclonus syndrome with autoantibodies after immune-checkpoint inhibitor treatment has not been reported previously. Although a causal relationship between immune-checkpoint inhibitors and paraneoplastic syndromes has been suggested, the mechanism remains unknown.

The acute effects of glycemic control on nerve conduction in human diabetics.

OBJECTIVE: To investigate acute changes in nerve conduction associated with glycemic control. In diabetes, nerve dysfunction can result from reversible metabolic factors associated with hyperglycemia, as well as structural changes. METHODS: Multiple nerve conduction parameters including F-wave latencies were measured in 47 diabetic patients with prominent hyperglycemia before and after intensive insulin treatment. RESULTS: Four weeks after the start of treatment, there was a significant improvement in minimal F-wave latencies of the median (P<0.001) and tibial (P<0.001) nerves, and in distal latencies (P=0.01) and sensory nerve conduction velocities (P<0.001) of the median nerves. Amplitudes of motor and sensory responses did not change significantly. These findings were similar for patients with type 1 (n=8) and those with type 2 (n=39) diabetes. Patients with poorer glycemic control or milder neuropathy tended to show greater changes after treatment. CONCLUSIONS: Glycemic control quickly alters the speed of nerve conduction. F-wave latencies and conduction times across the carpal tunnel are very sensitive parameters. SIGNIFICANCE: Serial nerve conduction studies can detect reversible slowing of nerve conduction presumably caused by metabolic factors, such as decreased Na+/K+-ATPase activity, the altered polyol pathway, and tissue acidosis.

[A patient with coccidioidal meningoencephalitis].

A 37-year-old man presented with coccidioidal meningoencephalitis (CM) 1 month after a preceding case of pneumonia. Initially, he could not be definitely diagnosed with CM because of nonspecific features of the clinical, laboratory, and radiological findings. However, we began to suspect CM because the patient had lived in endemic area of coccidioidomycosis, and our subsequent analysis provided evidence of complement-fixing antibodies for Coccidioides immitis in serum and CSF, leading us to a final diagnosis. The CM was intractable, despite intensive administration of fluconazole and amphotericin B. Although the patient's CM gradually and mildly improved, he also suffered from bacterial meningoencephalitis and left putaminal hemorrhage with intraventricular hematoma, which caused persistent right hemiparesis and dementia. The incidence of coccidioidomycosis in Japan is rapidly increasing. The initial clinical manifestation of coccidioidomycosis is usually pneumonia, which in most cases heals spontaneously. Coccidioidomycosis rarely presents with meningoencephalitis, which is thought to be fatal. Immediate and adequate initiation of anti-fugal treatment is necessary to obtain a better prognosis for CM. Careful history-taking after a foreign trip is helpful when there is a suspicion of coccidioidomycosis.

Cutaneous sympathetic function and cardiovascular function in patients with progressive supranuclear palsy and Parkinson's disease.

Some procedures, such as deep inspiration, increase sweat output (SSwR; sympathetic sweat response) and reduce cutaneous blood flow (SVR; skin vasomotor reflex) on the palm. We investigated SSwR, SVR, and cardiovascular function in 12 patients with progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 9 healthy subjects. In the PSP patients, SSwR was severely diminished, whereas SVR was maintained and cardiovascular function was well preserved. In the PD patients, SSwR was relatively preserved, SVR was maintained, and some patients showed cardiovascular hypofunction. A combination of skin sympathetic and cardiovascular tests may be useful for distinguishing between PD and PSP.

SPECT abnormalities with unilateral arm dystonia in a young mentally retarded apprentice cook: contralateral thalamo-cortical dysfunction.

We report a young, mentally retarded apprentice cook with a 2-month history of right upper extremity dystonia, for whom diazepam therapy was efficacious. We evaluated brain perfusion by single photon emission tomography (SPECT) before and after diazepam treatment. The abnormal hyperperfusion in the left thalamus and hypoperfusion in the left frontal cortex were normalized on the second SPECT under the successful diazepam treatment. These findings were indicative of functional changes in the left thalamus and left frontal cortex.

Anti-aquaporin-4 antibody-seronegative NMO spectrum disorder with Baló's concentric lesions.

A 34-year-old woman developed simultaneous bilateral severe optic neuritis and subsequent myelitis. Two months after the first attack, she developed a headache and dysesthesia in the left arm. Brain magnetic resonance imaging revealed multiple hyperintense lesions in the white matter of the right hemisphere, some of which were Baló-like concentric lesions. Our diagnosis was neuromyelitis optica spectrum disorder with Baló's concentric sclerosis (BCS), although the patient was negative for anti-aquaporin-4 (anti-APQ4) antibodies. Our case suggests that Baló's concentric sclerosis overlaps with neuromyelitis optica spectrum disorder and that this overlapping is caused by a mechanism that does not involve anti-AQP4 antibodies.

Cutaneous sympathetic function in patients with multiple system atrophy.

Some procedures increase the sweat output (SSwR; sympathetic sweat response) and reduce the cutaneous blood flow (SVR; skin vasomotor reflex) in the hand. We evaluated SSwRs and SVRs to deep inspiration, mental arithmetic, exercise, and tactile stimulation in 40 MSA patients and 15 healthy controls. We also conducted head-up tilt tests and R-R interval variation tests (CV(R-R)). SSwRs were present in all controls, but absent in 19 (47.5 %) of the MSA patients. The mean SSwR amplitudes in the MSA group were significantly lower than those in the control group. SVRs were evoked in all subjects except 3 MSA patients. There were no marked differences in SVR amplitudes between the two groups. Orthostatic hypotension and low CV(R-R) values were seen in 18 (45 %) and 13 (32.5 %) of the MSA patients, respectively. SSwR amplitudes correlated significantly with postural fall in blood pressure and CV(R-R) values in the MSA group. SSwRs were absent in about half of the MSA patients, and the SSwR results correlated with those of the cardiovascular autonomic tests. The SVRs were not severely disturbed in the MSA patients. We considered SSwR a useful index for the detection of autonomic dysfunction in MSA.

The acute effects of glycemic control on axonal excitability in human diabetics.

In diabetic nerves, the activation of the polyol pathway and a resulting decrease in Na(+)-K(+) ATPase activity lead to intra-axonal Na(+) accumulation and a smaller Na(+) gradient across the axolemma than normal. To investigate whether glycemic control is associated with acutely reversible changes in axonal excitability and Na(+) conductance, we measured the multiple excitability indices (strength-duration time constant, rheobase, refractoriness, and refractory period) of the median motor axons of 21 diabetic patients before and after intensive insulin treatment. Within 4 weeks after treatment was begun, there was a significant improvement in nerve conduction velocities, associated with increased strength-duration time constant, decreased rheobase, increased refractoriness, and prolonged refractory periods. Assuming that the strength-duration time constant partly reflects persistent Na(+) conductance, and that refractoriness/refractory periods depend on inactivation of transient Na(+) channels caused by prior depolarization (the influx of Na(+)), the patterns of changes in these indices may reflect a reduced trans-axonal Na(+) gradient during hyperglycemia and its restoration by glycemic control in diabetic patients. Measurement of the excitability indices could provide new insights into the pathophysiology of human diabetic neuropathy.