Autophagic vacuolar myopathy (AVM) is an entity defined by the presence of autophagic vacuoles on muscle pathology. There are two emerging categories in AVM in addition to the best characterized Pompe disease.
One is Danon disease and its related disorders, which are characterized by autophagic vacuoles with unique sarcolemmal features (AVSF). AVSF express virtually all sarcolemmal proteins, in addition to acetylcholinesterase, on their vacuolar membranes. Danon disease is caused by primary deficiency of a lysosomal membrane protein, LAMP-2. Interestingly, in this disease, the number of AVSF increases as the patients age. Other AVSF myopathies include X-linked myopathy with excessive autophagy which is now known to be caused by VMA21 mutations.
The other AVM is typified by the presence of rimmed vacuoles, which are actually clusters of autophagic vacuoles on electron microscopy. One of the well known diseases in this group is distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy (HIBM). DMRV is caused by mutations in GNE gene that encode a rate-limiting enzyme in the sialic acid biosynthetic pathway. Interestingly, in DMRV model mice, sialic acid supplementation almost completely precluded the disease phenotype, indicating that decreased sialic acid is the cause of myopathic phenotype and sialic acid supplementation can prevent the disease process.
Interestingly, both genetically diagnosable AVSF myopathies are primarily due to lysosomal dysfunctions. In contrast, rimmed vacuoles are secondarily caused by extra-lysosomal defects, such as hyposialylation in DMRV/HIBM, and are formed at later stages of the disease.

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A 50-year old woman, who had consanguineous parents, developed gait disturbance at age 3, and revealed nystagmus, cerebellar ataxia, peripheral neuropathy, and spastic tetraparesis. She admitted to our hospital at age 14, and the symptoms progressed very slowly. MRI of this case at age 45 showed a remarkable, diffuse hypomyelination of the cerebrum. Her older sister who already deceased at age 16 showed neurological symptoms similar to this case. The patient was found to have no proteolipid protein-1 gene duplications and deletions and base substitution. Her symptoms were considered to be different from those of typical HLD2, 3, 4 and 5. She carried no GJA12 mutations. These facts suggested that this disease is a novel, autosomal recessive hypomyelinating leukodystrophy.

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A 65-year-old woman showed progressive asymmetric sensory ataxic neuropathy (SAN) in upper limbs over 12 years, beginning with the onset of primary biliary cirrhosis (PBC). Nerve conduction study showed that sensory action potential was not evoked in upper limbs. Right superficial radial nerve biopsy showed the density of myelinated fibers was severely decreased with large-fiber predominance. Since Sjögren's syndrome (SjS) and paraneoplastic syndrome were denied, this type of neuropathy seems accompanied with asymptomatic PBC. Corticosteroid administration and intravenous immunoglobulin therapy failed to obtain any beneficial effect. The pathological mechanism is considered ganglionitis, which resembles that found in association with SjS. We should also consider PBC as the cause of SAN.

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We report a 64-year-old man diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) associated with pulmonary squamous cell carcinoma. Circulating anti-P/Q-type voltage-gated calcium channel (VGCC) antibody was detected, and the patient was treated with 3,4-diaminopyridine. At age 61, chest radiograph revealed a tumor shadow in the right upper lung field. This was surgically removed, and a histological diagnosis of moderately differentiated pulmonary squamous cell carcinoma was obtained. After about 1 year, mediastinal metastasis was detected and 5-FU was administered. Eight months later, metastasis was noted in the left frontal hemisphere, and radiosurgical therapy was performed. The brain tumor gradually shrank, but generalized fatigue, thirst, and gait disturbance developed after 4 months. A diagnosis of LEMS was made on the basis of neurological findings including proximal muscle weakness and absent tendon reflexes; autonomic symptoms (thirst, constipation, and impotence); characteristic electromyographic findings; and circulating anti-P/Q-type VGCC antibody. He has been treated with 3,4-diaminopyridine at a dose of 30mg/day, resulting in marked improvement in symptoms but little change in electromyographic findings. The present case is very rare and suggests that anti-P/Q-type VGCC antibody may be involved in the mechanism of LEMS associated with pulmonary squamous cell carcinoma.

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A 26-year-old woman with primary amenorrhea in association with hypergonadotropinism, and lacking a vagina and uterus, suffered from a gradually progressive gait disturbance in her adolescence. The patient has no family history of ataxia and a chromosome study showed a normal karyotype (46,XX). Using the revised Hasegawa Dementia Scale, her cognitive function was measured as that of a normal adult, however, neurological examination revealed symptoms of scanning speech, horizontal gaze-evoked nystagmus, and ataxia. Bulging eyes, high-arched palate, scoliosis and ventricular septal defect were also observed. A brain MRI showed atrophy of the cerebellum. A ¹²³I-IMP brain SPECT study showed hypoperfusion in the cerebellum.
Previous studies show that among patients with cerebellar ataxia and hypergonadotropic hypogonadism, some show an autosomal recessive inheritance, while others have no family history. As a cause, a chromosomal abnormality is unlikely because all reported karyotypes were normal. This case is different from other reported cases in that she is not mentally impaired or deaf. The present case indicates that there is a close relationship between cerebellar ataxia and hypogonadism, and that other symptoms such as deafness and mental impairment could be an additional variable in patients with cerebellar ataxia and hypergonadotropic hypogonadism.

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We describe two patients who developed progressive ascending paralysis associated with Guillain-Barré syndrome (GBS) during late pregnancy. A 25-year-old woman in the 30th week of gestation (GW) developed diarrhea followed by GBS and weakness of the bilateral facial muscles. Serum IgM antibody titers against cytomegalovirus (CMV) were high. Respiratory insufficiency developed at GW 31 requiring cesarean section and artificial ventilation. The facial palsy and limb paralysis persisted thereafter. Serum anti-GM2 IgM and anti-GalNAc-GD1a IgM antibodies were positive so immunoadsorption therapy (IAT) was applied. These antibody titers decreased with clinical improvement after IAT. The baby was healthy and did not have CMV. The other patient was a 24-year-old woman at GW 28 in whom GBS developed after a common cold. Right facial muscles were also weak and serum anti-GM2 IgM antibody was positive. Cesarean section was performed because of uterine bleeding. The clinical findings improved thereafter and the baby was healthy. The findings show that the course of GBS that develops after CMV infection can be severe and accompanied by respiratory insufficiency.

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It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22^nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30^th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of NMO during pregnancy.

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A case of spontaneous intracranial hypotension (SIH) with extensive epidural fluid collection in the spine is described. Although epidural blood patch (EBP) was not performed, treatment with glucocorticoid resulted in clinical and radiological improvement.
A previously healthy 45-year-old woman developed severe generalized headache that was partially relieved by lying flat (day 1). On day 5, she consulted our clinic. Neurological examination was unremarkable. Lumbar cerebrospinal fluid (CSF) pressure was too low to be measured. On day 11, cranial MRI with gadolinium-DTPA infusion demonstrated diffuse thickening and enhancement of the pachymeninges. Radionuclide cisternography demonstrated early accumulation of the tracer in the bladder but there was no sign of CSF leakage. Spinal MRI showed epidural fluid collection extending from the upper cervical through lumbar levels, suggesting that lumbar EBP might be less effective. Three weeks of bed-rest and oral hydration failed to relieve the headache. Oral prednisolone 40mg was started on day 23, and the headache improved within two days. Cranial MRI on day 88 showed complete resolution of the previous abnormalities. Spinal MRI on day 118 demonstrated almost complete disappearance of epidural fluid collection.
The present case suggests that glucocorticoid therapy can be a useful treatment option for SIH.

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After the Cancer Control Act (Basic Act) was enforced in April of 2007, the Ministry of Health, Labour and Welfare and local governments nominated leading hospitals (1 chief center in every prefecture, and 1 core hospital in every secondary medical area) for comprehensive promotion of research, prevention and treatment of cancers. These hospitals are supposed to organize palliative care seminars at least once every year to conduct basic training on palliative care for all doctors engaged in cancer treatment, in order to implement palliative care from the early stage. The seminar contains lectures and role-plays regarding relief of pain and improving quality of life during recuperation for all cancer patients and their families. The author suggests that neurologists attend such seminars and introduce similar skills and knowledge to patients with neurological diseases, particularly intractable diseases, after the author had occasion to join such a seminar as an assistant facilitator. The training sessions for communication with patients and families, giving bad news, using opioids, and organizing support teams among local resources also seem useful for neurological fields, until similar teaching schemes are established by appropriate organizations, such as the Japanese Society of Neurology.

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