Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study.

BACKROUND: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients. METHODS: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge. RESULTS: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups. CONCLUSION: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.

Review article: coeliac disease in later life must not be missed.

BACKGROUND: The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. AIM: To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. METHODS: To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. RESULTS: Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. CONCLUSIONS: Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.

Down syndrome in adults: a 27-year follow-up of adaptive skills.

In 1988, we assessed the adaptive skills of 45 adults with Down syndrome (DS) (21 women and 24 men, age 20-58) with the Portage scale. Since then, we have followed them and also screened for signs of clinical dementia with the Present Psychiatric State - Learning Disabilities assessment. The mean adaptive age (AA) of the study group decreased with increasing age; the age of 35 being the turning point in the clinical course of DS. The mean AA was 4.4 years between ages 20 and 34, 3.4 years between ages 35 and 49, and 2.4 years between ages 50 and 66. Inter-individual variation was, however, large. Between ages 20 and 25, the AA of the study subjects ranged from 2.3 to 6 years; and after the age of 50, from 0.3 to 4.8 years. By the end of the study, all subjects showed signs of clinical dementia. These appeared most frequently as reduced self-care skills, loss of energy, forgetfulness, and impaired understanding. We found no connection between apolipoprotein E genotype and the clinical course of DS. We recommend follow-up of adaptive skills and screening for dementia signs in adults with DS.

Gliadin antibodies in older population and neurological and psychiatric disorders.

OBJECTIVES: A variety of neurological and psychiatric disorders have recently been linked to coeliac disease and gluten sensitivity. We here explored whether persistently positive gliadin antibodies (AGA) and coeliac-type HLA increase the risk of gluten sensitivity-related neurological and psychiatric manifestations. The study was carried out in an older population who had consumed gluten for decades but who had no previous coeliac disease diagnosis. MATERIALS AND METHODS: The original study population comprised 4272 randomly selected older individuals, of whom 2089 had AGA and transglutaminase 2 antibodies (antiTG2) measured twice within a 3-year interval. Forty-nine persistently AGA-positive but antiTG2-negative subjects with coeliac-type HLA and 52 randomly selected persistently AGA- and antiTG2-negative age- and sex-matched controls were clinically examined for neurological disorders. The Psychological General Well-Being (PGWB) questionnaire, the SF-36 health survey questionnaire and the Depression Scale (DEPS) were employed to evaluate psychological well-being. The medical files of all the study subjects were analysed for previous illnesses. RESULTS: Persistently AGA-positive but antiTG2-negative older subjects carrying coeliac disease-type HLA did not evince significantly more neurological symptoms or diseases than AGA-negative control subjects (P = 0.682, P = 0.233). There were no statistically significant differences between AGA-positive and AGA-negative groups in psychological well-being and quality of life when measured by PGWB (P = 0.426), SF-36 questionnaires (P = 0.120) and DEPS (P = 0.683). CONCLUSIONS: At population level, persistent AGA positivity did not indicate gluten sensitivity-related neurological and psychiatric disorders.

POLG1 manifestations in childhood.

OBJECTIVE: Mitochondrial DNA polymerase γ (POLG1) mutations in children often manifest as Alpers syndrome, whereas in adults, a common manifestation is mitochondrial recessive ataxia syndrome (MIRAS) with severe epilepsy. Because some patients with MIRAS have presented with ataxia or epilepsy already in childhood, we searched for POLG1 mutations in neurologic manifestations in childhood. METHODS: We investigated POLG1 in 136 children, all clinically suspected to have mitochondrial disease, with one or more of the following: ataxia, axonal neuropathy, severe epilepsy without known epilepsy syndrome, epileptic encephalopathy, encephalohepatopathy, or neuropathologically verified Alpers syndrome. RESULTS: Seven patients had POLG1 mutations, and all of them had severe encephalopathy with intractable epilepsy. Four patients had died after exposure to sodium valproate. Brain MRI showed parieto-occipital or thalamic hyperintense lesions, white matter abnormality, and atrophy. Muscle histology and mitochondrial biochemistry results were normal in all. CONCLUSIONS: POLG1 analysis should belong to the first-line DNA diagnostic tests for children with an encephalitis-like presentation evolving into epileptic encephalopathy with liver involvement (Alpers syndrome), even if brain MRI and morphology, respiratory chain activities, and the amount of mitochondrial DNA in the skeletal muscle are normal. POLG1 analysis should precede valproate therapy in pediatric patients with a typical phenotype. However, POLG1 is not a common cause of isolated epilepsy or ataxia in childhood.

Undetected coeliac disease in the elderly: a biopsy-proven population-based study.

BACKGROUND: Up to 1% of the population suffer from coeliac disease. Data on the prevalence in elderly people is scant. We hypothesized that they would over time have developed obvious symptoms. Clinically silent or undiagnosed disease would thus be relatively uncommon. AIMS: To evaluate the prevalence of coeliac disease in elderly people. METHODS: The study comprised 2815 individuals aged 52-74 years. Clinical cases of coeliac disease were recorded. Sera from all subjects were screened by IgA class tissue transglutaminase antibodies, and seropositive underwent small bowel biopsy. RESULTS: Coeliac disease was detected in altogether 60 individuals, in 25 (0.89%) on clinical grounds, and screening found in 35 (1.24%) new biopsy-proven cases. Thus, a total prevalence of 2.13% (95% confidence intervals 1.60-2.67%) was reached. Of the screen-detected cases, 15 had symptoms, albeit mostly mild. Two out of the 60 had small bowel T-cell lymphoma and two had gastric cancer. The total frequency of biopsy-proven coeliac disease and seropositive cases without histological confirmation was 2.45% (1.88-3.02%). CONCLUSION: The prevalence of coeliac disease in elderly people was higher than what has been reported in the population in general. Active case finding by serologic screening is encouraged, since undetected cases may be prone to increased morbidity and mortality.

Neuromuscular and sensory disturbances in patients with well treated coeliac disease.

OBJECTIVES: A body of evidence shows that coeliac disease is associated with protean manifestations outside the intestine, and neurological disorders are well recognised. However, it remains obscure whether there are signs of clinical or subclinical nervous system involvement even in patients adopting an adequate gluten free diet. The aim of this study was to assess in a controlled study whether patients with treated coeliac disease carry an increased risk for neuropathy and characterise the type of possible neuropathy. METHODS: Electroneuromyographic findings and vibration, thermal, and tactile thresholds of 26 patients with coeliac disease and 23 patients with reflux disease were analysed. RESULTS: Six (23.1 %) coeliac disease patients and one (4.3 %) reflux disease patient showed findings of chronic axonal neuropathy in quantitative needle EMG. In addition, two coeliac disease patients showed findings suggestive for myopathy. There were no significant differences in warm, cold, or vibration thresholds between the groups but means of heat pain thresholds and tactile thresholds were significantly higher in coeliac patients than in controls. CONCLUSION: An increased occurrence of axonal neuropathy was observed in well treated coeliac disease. This further indicates that neurological manifestations occur even in patients without overt malabsorption.

Association between coeliac disease, epilepsy and brain atrophy.

Patients with epilepsy and posterior cerebral calcifications have an increased risk of coeliac disease (CD). The occurrence of this syndrome and the overall risk of CD and epilepsy remain still poorly understood. This study presents the prevalence of CD, brain atrophy, and cerebral calcifications in patients with epilepsy of unknown aetiology. The medical records of 900 consecutive adult patients with epilepsy diagnosis were reviewed. The occurrence of CD in living patients with epilepsy of unknown aetiology (n = 199) was investigated; all patients without previously known CD were asked for serological screening for the disease and the diagnosis was verified with small bowel biopsy. The presence of occipital calcifications and brain atrophy in all available CT scans (n = 130) was evaluated. Five of 199 cases had prior history of CD. The prevalence of definite CD in the patients was 2.5% (5/199), which is significantly higher that the current prevalence of CD in our area (0.27%). Antibody testing and small bowel biopsy in positive cases failed to increase prevalence of CD. Eleven (8.5%) patients had intracerebral calcifications and 3 of them posterior calcifications; all 11 had negative screening results for CD. Four (80%) patients with definite CD had supratentorial brain atrophy compared with 33 (26%) of 125 patients without CD. Prevalence of CD was increased among patients with epilepsy of unknown aetiology, but the combination of CD, epilepsy and intracranial posterior calcifications was rare in Finnish adult epilepsy population.

Coeliac disease in patients with cerebellar ataxia of unknown origin.

BACKGROUND: Neurological symptoms of unknown origin are common in coeliac disease (CD). Evidence suggests that CD may also contribute to the development of idiopathic late-onset ataxia. AIM: To evaluate the frequency of CD in patients with cerebellar ataxia of unknown origin. METHODS: The medical files of adult patients with the diagnosis of cerebellar ataxia of unknown origin (n=44) were evaluated. Serum gliadin, endomysial, and serum tissue transglutaminase antibodies were used as screening tests for CD. Subjects with positive results were referred to small-bowel biopsy. RESULTS: The frequency of CD was as high as 9.1% in all patients. A thorough interview and review of the patient files indicated alcohol abuse as a cause for cerebellar disease in almost half (45.5%) of our patients. When the cases with alcohol abuse were omitted, the calculated frequency of CD was 16.7% in patients with ataxia of unknown origin. CONCLUSION: CD is a common association with cerebellar disease and the disease should be considered in all patients with ataxia of unknown origin.

Mixed connective tissue disease associated with chronic inflammatory demyelinating polyneuropathy.

We present a patient with mixed connective tissue disease (MCTD) and slowly progressing demyelinating polyradiculoneuropathy (CIDP). To our knowledge, the case described is the first reported MCTD case associated with definite CIDP.

Coeliac disease presenting with neurological disorders.

It is well known that coeliac disease may be associated with various neurological manifestations. We have had a high index of suspicion of coeliac disease during recent years in our neurological clinic. As a result 10 (7%) out of 144 of our new coeliac patients were detected because of neurological symptoms. The most common neurological manifestations were neuropathy, memory impairment and cerebellar ataxia. In these patient groups screening for coeliac disease with serological antibody tests helps to find patients who may suffer from this disease.

Pulmonary expression of glutathione S-transferase M3 in lung cancer patients: association with GSTM1 polymorphism, smoking, and asbestos exposure.

To characterize the relative roles of glutathione S-transferases (GST) M1 and M3 in the susceptibility to lung cancer, the pulmonary expression of GSTM3 was quantified immunochemically and related to the GSTM1 genotype in 100 lung cancer patients. Among active smokers and recent ex-smokers (for 6 years or less), parenchymal GSTM3 expression was lower in patients with a homozygous GSTM1 null genotype than in those who were GSTM1 positive and had similar smoking habits (P < 0.001 and P = 0.004, respectively). However, in long-term ex-smokers (for 15 years or longer) GSTM3 was not affected by the GSTM1 genotype. Among active smokers and recent ex-smokers who were homozygous GSTM1 null, those with a definite or probable exposure to asbestos expressed GSTM3 at significantly higher levels than those for whom it was unlikely (P = 0.04). A similar effect of the homozygous GSTM1 null genotype on GSTM3 expression was not detected in the bronchial epithelium when GSTM3 was visualized immunohistochemically. Different mechanisms may result in an increased risk of either squamous cell or adenocarcinomas in patients with the homozygous GSTM1 null genotype. Low expression of GSTM3 due to smoking in the parenchymal lung of GSTM1 null individuals can theoretically favor the development of adenocarcinoma. Our data indicated a predominance of this tumor type in patients with low expression of GSTM3.