Reduction of a vascular endothelial growth factor receptor, fetal liver kinase-1, by antisense oligonucleotides induces motor neuron death in rat spinal cord exposed to hypoxia.

Vascular endothelial growth factor (VEGF) is reported to play a neuroprotective role through a VEGF receptor, fetal liver kinase-1 (Flk-1) in vitro. We investigated whether reduction of Flk-1 could induce motor neuron loss in rat spinal cord by inhibiting the expression of Flk-1 in rat spinal cord using antisense oligodeoxynucleotides (ODNs) against the Flk-1 receptor. Rat spinal cord was repetitively exposed to 12% hypoxia, and the change of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the mitogen-activated protein kinase kinase (MEK)/extracellular-signal-regulated kinase (ERK) pathway was examined. Intrathecal infusion of Flk-1 antisense ODNs for 7 days suppressed almost completely Flk-1 expression in the lumbar segment of the spinal cord and was followed by a hypoxic challenge with 12% oxygen for 1 h that was repeated for 7 more days. In the lumbar segment, we observed that reduced Flk-1 expression and hypoxic challenge for 7 days resulted in approximately 50% loss of motor neurons, in which the activation of Akt and ERK, that is, increased levels of phosphorylated-Akt and of phosphorylated-ERK by hypoxia, was markedly inhibited. In contrast, the reduction of Flk-1 expression alone did not induce motor neuron loss. These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways.

Nocturnal blood pressure dip in CADASIL.

The influence of a nocturnal blood pressure dip on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has not yet been clarified. We attempted to examine a correlation with the nocturnal blood pressure dip and CADASIL. We monitored circadian blood pressure patterns by the use of a portable blood pressure monitoring device in five patients with CADASIL and 10 age- and sex-matched control subjects. Based on nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP > or =20%), dippers (> or =10% but <20%), nondippers (<10% but > or =0%), and inverted dippers (<0%). Three patients revealed non-dipper and two inverted dipper. Nighttime MABP fall was significantly lower in patients compared with control subjects (P<0.01). This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence and/or worsening of deep white matter lesions in CADASIL.

Rheumatoid factor positive hypertrophic cranial pachymeningitis in association with hypopituitarism and multiple cranial nerve palsies.

This is the first report of a patient presenting with rheumatoid factor (RF) positive hypertrophic cranial pachymeningitis (HCP) in association with hypopituitarism and multiple cranial nerve palsies. Our patient developed palsies of the left II and III, bilateral VI and VII, and right IX, X, and XII cranial nerves. A stimulation test showed hypopituitarism due to hypothalamic failure. The patient was seropositive for RF but had no multiple joint pain or deformities. Magnetic resonance imaging (MRI) showed thickened dura of the sellar and parasellar region, hypothalamus, bilateral cavernous sinuses and the tentorium all of which were enhanced by gadolinium (Gd). Treatment with prednisone improved clinical symptoms and MRI findings concomitant with reduction of RF titer. Although the exact mechanism of HCP has not been clearly elucidated, the present case suggests an autoimmune mechanism associated with RF.

Serial MRI findings in patient with chronic cryptococcus meningo-encephalitis.

We describe the serial changes of magnetic resonance imaging (MRI) in a patient with chronic cryptococcus meningo-encephalitis. In the subacute phase, MRI revealed a focal lesion with hyperintensity on T2-weighted image (WI) in the left thalamus. At 11 months after the onset, MRI showed a focal lesion with hyperintensity on T2-WI in the right pons that was enhanced with gadolinium (Gd). At 13 months after the onset, the lesion in the left thalamus became rim enhanced with Gd. After antifungal therapy (amphotericin B and 5-flucytosine), the rim enhancement in the left thalamus and the high signal intensity area in the right pons decreased. Cryptococcoma should be in the differential from other ring enhancing lesions.

Two cases of Japanese CADASIL with corpus callosum lesion.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. In the present study, a Japanese CADASIL family was first reported with missense mutation of Arg141Cys of Notch3 and a unique lesion of corpus callosum. Upon neuropsychological examination, our case 1 showed only right-handed constructional apraxia associated with corpus callosum lesion. No other callosal disconnection signs were present. Sagittal T2 weighted image of case 1 showed multiple small lesions along with the pericallosal branches from the truncus to the posterior part of the splenium in the corpus callosum. Although detailed mapping of the corpus callosum for functional fractionation in humans remains incomplete, the constructional apraxia on the right may be related to callosal dysfunction from the truncus to the posterior part of the splenium in the corpus callosum.

[A case of neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions].

We report a 55-year-old woman with neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions. She showed a cryptogenic high fever and cerebral cortical symptoms such as perseveration, limbkinetic apraxia and dementia. CSF study showed an increase of cell count and protein and a decrease of sugar. MRI showed diffuse T2-high signal intensity mainly in the subcortical white matter of left parieto-occipital lobes and basal ganglia. Her clinical signs greatly improved after administration of prednisolone. Her HLA type was not B51 but B54. Though our patient did not completely satisfy clinical criteria for neither neuro-Behçet's disease nor Sweet's syndrome, she showed partial features of both Behçet's disease and Sweet's syndrome.

[Familial pure akinesia].

We report a 67-year-old man and his family presenting pure akinesia (PA). He developed bradykinesia. A neurological examination showed a lack of facial expression but no tremor or rigidity. His eye movement was full, and he had frozen gait and pulsion symptoms. There was no evidence of dementia. Levodopa therapy was not effective. Magnetic resonance imaging revealed no brainstem and cerebellar atrophy. 99mTc-ECD-SPECT had no further abnormality. His father and brother had similar symptoms as him. We conclude that this family is the first reported example of pure akinesia with autosomal dominant inheritance.