Neuralgia in the occipital region associated with ipsilateral trigeminal herpes zoster: Three case reports.

BACKGROUND: Nerve fibers related to pain and temperature sensation in the trigeminal nerve territory converge with the upper cervical spinal nerves from the level of the lower medulla oblongata to the upper cervical cord. This structure is called the trigemino-cervical complex and may cause referred pain in the territory of the trigeminal or upper cervical spinal nerves. CASE SERIES: Here, we report three cases of paroxysmal neuralgia in the occipital region with mild conjunctivitis or a few reddish spots in the ipsilateral trigeminal nerve territory. The patients exhibited gradual progression of these reddish spots evolving into vesicles over the course of several days, despite the absence of a rash in the occipital region. The patients were diagnosed with trigeminal herpes zoster and subsequently received antiherpetic therapy. Remarkably, the neuralgia in the occipital region showed gradual amelioration or complete resolution before the treatment, with no sequelae reported in the occipital region. DISCUSSION: The trigemino-cervical complex has the potential to cause neuralgia in the occipital region, as referred pain, caused by trigeminal herpes zoster. These cases suggest that, even if conjunctivitis or reddish spots appear to be trivial in the trigeminal nerve territory, trigeminal herpes zoster should be considered when neuralgia occurs in the ipsilateral occipital region.

[A case of recurrent myelitis associated with anti-myelin oligodendrocyte glycoprotein antibody that developed only as localized short spinal cord lesions].

A 65-year-old man initially developed numbness and hypesthesia in the right shoulder and brachial regions that disappeared within several months. MRI revealed a small lesion extending to a vertebral segment in the right dorsal region of the cervical spinal cord at the vertebral height of C2/3. About 15 months later, the intermittent lancinating pain identical to the right trigeminal and occipital neuralgia with pain and hypesthesia distributed in the right C2-C4 dermatome regions appeared. MRI revealed a new oval lesion with gadolinium enhancement in the right dorsal region of the cervical spinal cord at the vertebral height of C1, which was thought to involve the posterior column and lower part of the spinal tract nucleus of the trigeminal nerve. There was no optic nerve, brain, or other spinal cord lesions that suggested demyelination on MRI. A titer of serum anti-aquaporin-4 antibody was negative, but anti-myelin oligodendrocyte glycoprotein (MOG) antibody was found to be positive. The symptoms were relieved by corticosteroid treatment. Our report presents a rare case of anti-MOG antibody-positive recurrent myelitis that developed only as localized short upper cervical spinal cord lesions, not meeting the diagnostic criteria for neuromyelitis optica spectrum disorders.

An investigation into the effects and prognostic factors of cognitive decline following subthalamic nucleus stimulation in patients with Parkinson's disease.

We retrospectively investigated the effects of subthalamic nucleus stimulation (STN-DBS) on new postoperative onset of cognitive decline and prognostic factors for advanced Parkinson's disease (PD). We studied 39 PD patients who had received bilateral STN-DBS. Clinical symptoms, cognitive function, psychiatric function, and health-related quality of life (HRQOL) were assessed before and six months after surgery. Based on the results of neuropsychological examinations six months after the surgery, the subjects were divided into those with and those without cognitive decline. We compared pre- and post-operative assessments between the two groups. Prognostic factors were investigated using multiple logistic regression analyses. Seven patients had cognitive decline six months after the operation (17.9%); they were significantly older than those without cognitive decline. Preoperative neuropsychological examinations revealed impairments in language and executive function. No differences were found in clinical symptoms. Patients with cognitive decline had significantly worse apathy scale scores. The HRQOL revealed significant declines in the Mental Component Summary (MCS), vitality, and mental health (MH) domains. Postoperative comparisons revealed novel significant differences in activities of daily living in the "on" and "off" states and in daytime drowsiness. Preoperative differences seen in the MCS and vitality indices were no longer present. Word fluency, and apathy scale and MH scores were independent preoperative prognostic factors for cognitive decline. New postoperative onset of cognitive decline due to STN-DBS affected activities of daily living and psychiatric function. Preoperative non-motor symptoms may be prognostic factors for new onset of cognitive decline.

An autopsy case of superficial siderosis of the central nervous system accompanied by anterior sacral polycystic meningocele in neurofibromatosis type 1.

A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid-posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding source of the superficial siderosis in this patient. Bleeding from the meningocele might result from the vulnerability of vessel walls in NF1.

An autopsy case of frontotemporal lobar degeneration with the appearance of fused in sarcoma inclusions (basophilic inclusion body disease) clinically presenting corticobasal syndrome.

We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD-FUS), clinically presenting corticobasal syndrome (CBS). A 54-year-old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right-side dominant limb-kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left-dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb-kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA-binding protein-associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA-binding protein of 43 kDa (TDP-43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD-FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP-43 inclusions (FTLD-TDP), Pick's disease, Lewy body disease and CJD. However, FTLD-FUS (BIBD) has been rarely reported. Our case suggested further pathological heterogeneity in CBS than had previously been reported. It is necessary to consider FTLD-FUS (BIBD) as a background pathology for CBS in the future.

[Serial magnetic resonance images of a Creutzfeldt-Jakob disease patient with V180I mutation obtained over 10 years].

We acquired serial magnetic resonance images (MRIs) of a Creutzfeldt-Jakob disease (CJD) patient carrying the V180I mutation; his symptoms slowly progressed over a period of 10 years. A 57-year-old man presented with cognitive impairment and was admitted to our hospital. Diffusion-weighted images (DWIs) and fluid-attenuated inversion recovery (FLAIR) images showed high-intensity areas (HIAs) in the cerebral cortex and basal ganglia, but not in the thalamus, brainstem, and cerebellum, until 1.5 years after symptom onset. The HIAs in the cerebral cortex and basal ganglia disappeared 4 years after symptom onset, while the atrophy in these regions progressed rapidly during this period. However, the thalamus, brainstem, and cerebellum appeared to be preserved over 10 years after symptom onset. The mechanism for the regional vulnerability in brains of CJD patients remains unclear. Further studies in additional cases are required to clarify whether differences in the mutation of the prion protein gene might be associated with the vulnerability.

[Encephalomyelopathy due to vitamin B12 deficiency with seizures as a predominant symptom].

We report a 39-year-old man who developed seizures as a predominant symptom of vitamin B12 deficiency. About a month before admission to our hospital, he experienced flickering vision, and had generalized convulsive seizures about ten times a day. On admission, he presented with visual disturbance and paralysis of the left leg. Brain MRI revealed a tumor-like lesion in the medial side of the right frontal lobe. Follow-up MRI about 2 weeks after admission demonstrated multiple lesions in the periaqueduct, the medial side of the bilateral thalami, the bilateral frontal lobes, and the bilateral occipital lobes. After administration of antiepileptic drugs, his condition was well-controlled. Paralysis of his left leg was gradually improved, and abnormal findings on brain MRI disappeared except that in the right frontal lobe cortex, which was considered to be cortical laminar necrosis. 123I-IMP-SPECT showed hyperperfusion in the bilateral occipital lobes. About 3 months after the first admission, he was readmitted because of ataxic gait and numbness in the extremities. Laboratory tests revealed macrocytic anemia and vitamin B12 deficiency. Spinal MRI revealed typical findings of subacute combined degeneration. Brain MRI showed multiple new lesions in the bilateral dorsal sides of the medulla, cerebellar hemispheres, interthalamic adhesion, and left frontal cortex. After the initiation of vitamin B12 supplementary therapy, the symptoms were improved, and the abnormal MRI findings disappeared. Serum anti-gastric-parietal-cell antibody and anti-intrinsic-factor antibody were positive. 123I-IMP-SPECT demonstrated hypoperfusion in the bilateral occipital lobes, possibly reflecting visual disturbance. To the best of our knowledge, this is the first report indicating that vitamin B12 deficiency may insult various brain regions as well as the spinal cord with reversibility. Vitamin B12 deficiency should be also considered in the differential diagnosis of the causes of epilepsy.

Spatiotemporal recapitulation of central nervous system development by murine embryonic stem cell-derived neural stem/progenitor cells.

Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location of NS/PC origin. Here we demonstrate that we can recapitulate the spatiotemporal regulation of central nervous system (CNS) development in vitro by using a neurosphere-based culture system of embryonic stem (ES) cell-derived NS/PCs. This ES cell-derived neurosphere system enables the efficient derivation of highly neurogenic fibroblast growth factor-responsive NS/PCs with early temporal identities and high cell-fate plasticity. Over repeated passages, these NS/PCs exhibit temporal progression, becoming epidermal growth factor-responsive gliogenic NS/PCs with late temporal identities; this change is accompanied by an alteration in the epigenetic status of the glial fibrillary acidic protein promoter, similar to that observed in the developing brain. Moreover, the rostrocaudal and dorsoventral spatial identities of the NS/PCs can be successfully regulated by sequential administration of several morphogens. These NS/PCs can differentiate into early-born projection neurons, including cholinergic, catecholaminergic, serotonergic, and motor neurons, that exhibit action potentials in vitro. Finally, these NS/PCs differentiate into neurons that form synaptic contacts with host neurons after their transplantation into wild-type and disease model animals. Thus, this culture system can be used to obtain specific neurons from ES cells, is a simple and powerful tool for investigating the underlying mechanisms of CNS development, and is applicable to regenerative treatment for neurological disorders.

Disease progression of human SOD1 (G93A) transgenic ALS model rats.

The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies.

[Late-onset nonketotic hyperglycinemia: a case report].

We report a 66-year-old woman who developed mental deterioration in her school days, and progressive gait disturbance, dysarthria and bradykinesia in her 40 s. Her parents were consanguineous, and the two of her brothers were suspected to have the allied disorder. On physical examination, she was short-statured and high-arched palate was observed. Neurological examination revealed dementia, abnormal eye movement, dysarthria, spastic paraparesis with hyperreflexia, bilateral Babinski signs, cerebellar ataxia and dysuria. Brain MRI showed marked hypoplasia of corpus callosum with dilatation of lateral ventricles and cerebral sulci and significant cerebellar atrophy. Amino acid analyses showed significant elevation of glycine without ketosis in serum, cerebrospinal fluid, and urine, which lead us to the diagnosis of late-onset nonketotic hyperglycinemia(NKH). NKH is known to be a rare autosomal recessive metabolic disorder primarily caused by deficient activity of various components of the mitochondrial glycine cleavage system. Onset of the disease occurs most often in early infancy, however, later-onset variants have been described. Usually, late-onset NKH only manifests mild mental deterioration, character change, seizure, ataxia or spastic paraparesis, which sometimes makes difficulty in differentiating this disease from other hereditary cerebellar ataxia or spastic paraparesis. In addition, many structural brain abnormalities have been reported accompanied with NKH, and especially, agenesis or hypoplasia of corpus callosum is the most characteristic feature in this disease. Therefore, we emphasized that amino acid analyses should be considered in any patients who have cerebellar ataxia or spastic paraparesis of unknown cause with these neuroradiological findings.