[A patient with mesenteric lymphoma who developed amyotrophic lateral sclerosis and sepsis].

We treated a patient with mesenteric lymphoma who concomitantly developed amyotrophic lateral sclerosis (ALS). The patient died of urinary tract infection nine months after the onset of ALS. We herein report the changes in the patient's condition and the sequence of events until death from the viewpoint of a physiotherapist. The patient was a 69-year-old woman who developed mesenteric lymphoma in September of X year and perceived weakness in the toes in November of X year. She showed signs of upper and lower motor neuron disorders, and electrophysiologic testing revealed denervation in three areas of the spinal cord. In March of X+1 year, she was diagnosed with definite ALS based on the Awaji criteria. In April of X+1 year, she began to receive continuous home healthcare, specifically outpatient rehabilitation. No remarkable bulbar palsy was observed soon after the initiation of rehabilitation; however, manual muscle testing revealed strengths in the lower and upper limbs of 1 and 3-5, respectively, indicating muscle weakness and muscle atrophy. She developed exacerbation of neurological symptoms in the upper limbs, bulbar palsy, and respiratory muscle paralysis during rehabilitation. The ALS Functional Rating Scale-Revised indicated a decreased tendency to X [please define X]. In July of X+1 year, the mesenteric lymphoma had enlarged, resulting in the development of ureteric obstruction and ultimately causing hydronephrosis. Urinary tract infection and sepsis were diagnosed, and she was hospitalized. Although her fever temporarily subsided following ceftriaxone administration, she ultimately died due to a systemic inflammatory response syndrome three days after hospitalization. The mean period between the ALS onset and death is reportedly 40.6±33.1 months. The rate of ALS progression differs among individuals. Malignant tumors and paraneoplastic neurological syndrome may be involved in rapidly worsening neurological symptoms. Patients who concomitantly develop motor neuron disorders and malignant tumors are likely to have a higher risk of developing serious conditions associated with the exacerbation of neurological symptoms and complications. Our patient had several diseases that affected her survival prognosis; however, the sharing of information regarding her condition among healthcare professionals may have been insufficient. The primary physician responsible for treating each disease should cooperate with physiotherapists and other paramedical staff who have frequent opportunities to talk to patients in daily clinical practice. In geriatric patients in particular, such an environment is essential.

Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.

Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.

Churg-Strauss syndrome associated with hypersensitivity to acetaminophen.

Acetaminophen is a widely used antipyretic drug. We describe a 64-year-old Japanese woman who developed typical Churg-Strauss syndrome after frequent use of acetaminophen. Following the ingestion of acetaminophen, she exhibited various allergic reactions such as asthmatic attacks, pyrexia and petechiae on legs. In the lymphocyte transformation test, a positive reaction to acetaminophen was detected. A muscle biopsy revealed massive extravascular eosinophil infiltration and a necrotizing vasculitis. Hypersensitivity to acetaminophen may be implicated in the development of Churg-Strauss syndrome in this case.

Life style risks of Parkinson's disease: association between decreased water intake and constipation.

Gastrointestinal dysfunction, especially constipation, is one of the major problems in the daily life of patients with Parkinson's disease (PD). About 60 to 80% of PD patients suffer from constipation. Several studies have proven that constipation appears about 10 to 20 years prior to motor symptoms. More recently, Abbott et al. have found from a large scale prospective study that lower frequency bowel movements predict the future risk of PD. Furthermore, Braak et al. have found that Lewy neuritis and Lewy bodies, the hallmarks of PD pathology, appear in the dorsal nucleus of vagus in the earliest stage of the disease and then extend upward through the brain stem to reach the substantia nigra in the third stage. They also hypothesize that some yet undefined toxins break through the mucosal barrier of the intestine and are incorporated into the axon terminal of the vagus nerve and transported in a retrograde manner to the vagus nucleus. In this study, we assessed bowel movements and nutritional status in Japanese patients with PD. We found that intake of water was significantly decreased in PD patients from early life and associated with their constipation. Ninety four patients with PD (M 50, F 44) were enrolled. Nutritional status was assessed using the Self-administered Diet History Questionnaire (DHQ). Total water intake was calculated from the consumption of coffee, green tea, and tea. We also questioned the behavior of water drinking from the early stage of life. The questionnaire for bowel movements concerned the frequency of defecation, age of onset of constipation, and age of onset of motor dysfunction. Less than one bowel movement in 3 days was defined as constipation. The nutritional status of PD patients did not differ significantly from those of controls though several studies have shown excess intake of animal fats or reduced consumption of coffee are risks in PD. In contrast, water intake was significantly lower in PD patients than controls (604.0+/-377.2 ml/d vs 909.5+/-531.6 ml/d; P<0.0001). Interestingly, PD patients tended not to feel thirsty and thus they had no desire to drink water throughout their life. Seventy four patients out of 94 (78.7 %) complained of constipation. Mean bowel frequency was once per 3.3+/-1.1 days and 71.1% of patients were defined as having constipation. Women suffered from constipation more frequently than men (82.4% vs 61.9 %). In 33 patients out of 74 (44.6 %), onset of constipation preceded motor disturbance by an average time of 18.1+/-18.8 years. Furthermore, the amount of water intake correlated inversely with the severity of constipation and the depletion of water intake preceded constipation in most cases. The present results support previous findings that constipation precedes the onset of motor dysfunction in PD. To our knowledge, this is the first report to point out latent water depletion in PD patients. It is not certain at present whether coffee or caffeine themselves are the protective factor for PD or alternatively the amount of water in coffee drinking is more essential. Prospective studies on a large scale are necessary to elucidate the real meaning of water depletion in PD.