Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis.

OBJECTIVES: There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). In a transgenic mouse model of ALS, intrathecal infusion of insulin-like growth factor (IGF)-1 showed a promising increase in survival. We performed a double-blind clinical trial to assess the effect of intrathecal administration of IGF-1 on disease progression in patients with ALS. METHODS: Nine patients with ALS were randomly assigned to receive either a high dose (3 microg/kg of body weight) or low dose (0.5 microg/kg of body weight) of IGF-1 every 2 weeks for 40 weeks. The outcome measurements were the rate of decline of bulbar and limb functions (Norris scales) and forced vital capacity. RESULTS: The high-dose treatment slowed a decline of motor functions of the ALS patients in total Norris and limb Norris scales, but not in bulbar Norris or vital capacity. The intrathecal administration of IGF-1 had a modest but significant beneficial effect in ALS patients without any serious adverse effects. DISCUSSION: Intrathecal IGF-1 treatment could provide an effective choice for ALS although further studies in more patients are needed to confirm its efficacy and optimize dosages of IGF-1.

Localized lesions on MRI in a case of hypertensive brainstem encephalopathy.

We report a case of hypertensive brainstem encephalopathy (HBE) with unusual magnetic resonance imaging (MRI) findings. A 67-year-old woman presented with high blood pressure and stupor as the only symptoms. MRI revealed lesions localized in the area from the upper medulla oblongata to the lower pons with high fluid-attenuated inversion recovery (FLAIR) and T2-weighted signal intensity, but these were not seen in the whole brainstem and there were no accompanying occipital lobe changes. To our knowledge, no similar case has been reported. The lesions and symptoms dramatically improved after normalization of blood pressure. Severe hypertension that exceeded the range of autoregulation may have resulted in segmental vasodilatation and the increased vascular permeability may have lead to vasogenic edema in the localized areas of the brainstem.

Selective colocalization of transglutaminase-like activity in ubiquitinated intranuclear inclusions of hereditary dentatorubral-pallidoluysian atrophy.

To investigate the role of transglutaminase (TG) in the pathophysiology of dentatorubral-pallidoluysian atrophy (DRPLA), the distributions of ubiquitin-positive neuronal intranuclear inclusions (Ub-NII) and TG activity were studied in three patients with DRPLA and four disease controls. In the cerebellar granule cells of DRPLA, 2.5-4.9% of neurons had Ub-NII, and 7.5-9.8% of them were TG positive. In the frontal cortex; however, the ratio of neurons with Ub-NII was relatively low compared with those in the cerebellar cortex, and no Ub-NII was TG positive. There was no distinct difference in the ratio of neurons with Ub-NII and their TG positivity between the cases with homozygous or heterozygous DRPLA patients. The selective and good colocalization of Ub-NII and TG in the cerebellar granule cells may reveal a role of TG in the neurodegenerative process in DRPLA.

Potentiation of Akt and suppression of caspase-9 activations by electroacupuncture after transient middle cerebral artery occlusion in rats.

Electroacupuncture (EA) is an effective curative method for diseases including cerebral ischemia. In the current study, we investigated the effects of EA treatment on the activations of survival Akt and proapoptotic caspase-9 after 90 min of transient middle cerebral artery occlusion (tMCAO) in rat. Immunoreactivity of phospho-Akt (p-Akt) increased in the ipsilateral hemisphere after tMCAO with a peak at 8 h, and EA enhanced the Akt expression both in the number and the staining strength mainly in the ischemic penumbra (IP) at 8 and 24 h. Cleaved caspase-9 was strongly induced at 8 h in IP, which was suppressed with EA. The number of terminal deoxynucleotidyl transferase-mediated uridine 5' triphosphate-biotin nick end labelling positive cells reduced at 24 h in the cerebral cortex. These results suggest that EA potentiated the Akt and suppressed the caspase-9 activations, and may have a potential to reduce the number of neuronal cells undergoing apoptotic cell death.

Both conventional indices of cognitive function and frailty predict levels of care required in a long-term care insurance program for memory clinic patients in Japan.

AIM: To delineate relationships among cognitive function, frailty and level of care required in the Japanese long-term care insurance program (LTCIP) in outpatient memory clinic patients. METHODS: This was a cross-sectional study carried out at an outpatient memory clinic. Participants were 201 cognitively impaired patients. Cognitive function was measured by the Mini-Mental State Examination (MMSE). Frailty was measured by Timed Up & Go (TUG) and grip strength. Waist circumference, body mass index, living arrangement and level of care required in the LTCIP (rank 1 minor disability to rank 7 severe disability) were also assessed. RESULTS: Mean age, MMSE score, TUG score and grip strength were 78.8 ± 6.9 years, 19.6 ± 6.1, 14.6 ± 6.7 s and 16.9 ± 7.5 kg, respectively. A total of 70 patients (34.8%) had not applied for the certification, at least in part because of their younger age and existence of family caregivers. LTCIP rank was correlated both with MMSE score (ß: -0.49, P = 0.001), grip strength (ß: -0.27, P = 0.005) and living alone (ß: -0.18, P = 0.03), but not with TUG score (ß: 0.14, P = 0.105). CONCLUSION: In outpatients of a memory clinic, care ranks, which define the upper limit of monthly benefit in the Japanese LTCIP, were influenced by age, cognitive function, frailty and living arrangements. Understanding the relationship among these parameters would be useful in predicting the needs of cognitively impaired patients and important when comparing the possible services provided by long-term care systems for them worldwide.

Steroid-responsive encephalitis lethargica syndrome with malignant catatonia.

We report a 47-year-old man who is considered to have sporadic encephalitis lethargica (EL). He presented with hyperpyrexia, lethargy, akinetic mutism, and posture of decorticate rigidity following coma and respiratory failure. Intravenous methylprednisolone pulse therapy improved his condition rapidly and remarkably. Electroencephalography (EEG) showed severe diffuse slow waves of bilateral frontal dominancy, and paralleled the clinical course. Our patient fulfilled the diagnostic criteria for malignant catatonia, so we diagnosed secondary malignant catatonia due to EL syndrome. The effect of corticosteroid treatment remains controversial in encephalitis; however, some EL syndrome patients exhibit an excellent response to corticosteroid treatment. Therefore, EL syndrome may be secondary to autoimmunity against deep grey matter. It is important to distinguish secondary catatonia due to general medical conditions from psychiatric catatonia and to choose a treatment suitable for the medical condition.

Granulocytic sarcoma with orbit, cauda equina, muscle and peripheral nerve extension but without bone marrow involvement.

We report a very rare case of granulocytic sarcoma (GS) with muscle and peripheral nerve extension but without bone marrow involvement. A 53-year-old woman presented with sciatic pain and diplopia. Magnetic resonance imaging revealed bilateral orbital and cauda equina region tumors. The blood cell count, and bone marrow histology and cytology were normal. The characteristic cerebrospinal fluid (CSF) cytologic picture of CD14+, CD33+, CD4+, CD56+ and positive nonspecific erastase staining suggested the diagnosis of GS. The patient underwent intrathecal and systemic chemotherapy, as if she had acute myeloid leukemia (AML). This case emphasizes the value of CSF cytological examination and the use of an immunocytochemical marker.