[Managing End-of-Life Care in ALS and Its Associated Issue].

The neurological disease amyotrophic lateral sclerosis (ALS) requires pain palliation during end-of-life stages. From the view point of a home-care doctor who assists patients with their final wishes to die at home, I summarize the issues involving the section of medical treatments, the extent and frequency of end-of-life pain, the methodology of pain palliation, and the facts of end-of-life care at home. I also present several clinical cases of end-of-life home care and discuss its demand and problems.

Reduction rate of body mass index predicts prognosis for survival in amyotrophic lateral sclerosis: a multicenter study in Japan.

Malnutrition in the early stage has been reported as an independent predictor of survival in amyotrophic lateral sclerosis (ALS). We analyzed retrospectively the effect of variation of body mass index (BMI) on survival in ALS patients. In total, 77 consecutive ALS patients were enrolled from nine hospitals in Japan. Reduction rate of BMI was calculated from BMI before the disease onset and at the time of the first visit to each hospital. We analyzed the correlation between BMI reduction rate and total disease duration. Results showed that the median BMI reduction rate was 2.5 per year (interquartile range 1.3-3.8). The BMI reduction rate was significantly correlated with survival length (p <0.0001). There was also a significant difference in survival between ALS patients with a BMI reduction rate ≥ and < 2.5 (Kaplan-Meier survival analysis and the log-rank test, p < 0.0001; hazard ratio by the Cox model, 2.9816). In conclusion, faster reduction of BMI at the initial stage before the first visit to hospital predicts shorter survival length also in Japanese ALS patients.

[Palliative care at the end of life for intractable neurological diseases].

Palliative care at the end of life for intractable neurological diseases has come into discussion recently. According to the care guidelines for amyotrophic lateral sclerosis (ALS), suggested by the Japan Neurology Societies, neurological doctors should primarily aim at reducing patients' pain, share decisions with patients, and care for breathing difficulties, pain, and anxieties positively with the use of narcotics, like the care for cancer patients. Between June 2003 and June 2006, 58 of 79 patients (73%) refused a treatment to prolong their life, such as tracheal positive pressure ventilation (TPPV), and 19 of 24 (79%) patients desired to remain at home; these patients represented the majority. I will introduce the examples of ALS patients who refused TPPV, those who had intubation and ventilator attachment unwillingly at the time of emergency medical admission, and those who refused tube feedings. I will also report the practice on a patient with multi-system atrophy who was not self-decisive, the procedure of easing pain and its efficacy on the 9 ALS examples of home death, and the problems seen from 10 examples of death at a hospital. Hereafter, it is necessary to discuss intensely the problems of end-of-life palliative care especially for intractable neurological diseases in order to establish a methodology and to popularize it.

Unique cerebellar-cerebral form of autosomal recessive ataxia.

We describe a unique condition affecting two siblings with a form of progressive spinocerebellar ataxia. After a period of very slowly progressive ataxia, the patients developed an extremely accelerated progression of the condition which consisted of cerebellar ataxia, seizure, progressive dementia and spastic tetraparesis. Age of onset was variable at 7 to 18 years. Brain magnetic resonance image (MRI) showed marked atrophy of the cerebellum and cerebrum with strikingly preserved brainstem dimensions. Biochemical or molecular genetic analysis was performed in an elder sister and her parents to exclude known forms of familial spinocerebellar ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), progressive myoclonic epilepsy, and some metabolic disorders which could have a similar phenotype. The mode of inheritance appears to be autosomal recessive. We think that the affected siblings may have a new type of autosomal recessive cerebellar ataxia.

[Care and problems in intractable neurological diseases--home care of intractable diseases from the view of a practicing physician].

Taking into account how to care patients at home with intractable neurological disease and their family, I have introduced the achievement of the medical caring technique by an aged family member, the risks of the PEG and acute respiratory failures under BiPAP, the problems in home rehabilitation, and the experiences of home terminal care, from the view point of a practicing physician. Home caring pursues to support patients and their family to live peacefully with disease with highest quality of life. Hospice caring is also an important issue. From now on, I would like to try to give even better home care by early recognition of problems and by cooperating with hospitals, clinics and other field workers.

Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases.

We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.

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.