Cognitive decline in adult-onset temporal lobe epilepsy: Insights from aetiology.

PURPOSE: To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory decline would allow us to identify patients that would eventually benefit from more specific treatment. METHODS: Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up. RESULTS: Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65-596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively). CONCLUSIONS: Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.

Parkinson disease and Alzheimer disease: environmental risk factors.

INTRODUCTION: The purpose of this review is to update and summarise available evidence on environmental risk factors that have been associated with risk of Parkinson disease (PD) or Alzheimer disease (AD) and discuss their potential mechanisms. DEVELOPMENT: Evidence consistently suggests that a higher risk of PD is associated with pesticides and that a higher risk of AD is associated with pesticides, hypertension and high cholesterol levels in middle age, hyperhomocysteinaemia, smoking, traumatic brain injury and depression. There is weak evidence suggesting that higher risk of PD is associated with high milk consumption in men, high iron intake, chronic anaemia and traumatic brain injury. Weak evidence also suggests that a higher risk of AD is associated with high aluminium intake through drinking water, excessive exposure to electromagnetic fields from electrical grids, DM and hyperinsulinaemia, obesity in middle age, excessive alcohol consumption and chronic anaemia. Evidence consistently suggests that a lower risk of PD is associated with hyperuricaemia, tobacco and coffee use, while a lower risk of AD is associated with moderate alcohol consumption, physical exercise, perimenopausal hormone replacement therapy and good cognitive reserve. Weak evidence suggests that lower risk of PD is associated with increased vitamin E intake, alcohol, tea, NSAIDs, and vigorous physical exercise, and that lower risk of AD is associated with the Mediterranean diet, coffee and habitual NSAID consumption. CONCLUSIONS: Several environmental factors contribute significantly to risk of PD and AD. Some may already be active in the early stages of life, and some may interact with other genetic factors. Population-based strategies to modify such factors could potentially result in fewer cases of PD or AD.

[Wernicke's encephalopathy in non-alcoholic patients: a series of 8 cases]. / Encefalopatía de Wernicke en pacientes no alcohólicos: una serie de 8 casos.

INTRODUCTION: Wernicke's encephalopathy (WE) is an underdiagnosed condition, usually associated with alcoholism, and has a worse prognosis if there is a delay in diagnosis. A series of 8 non-alcoholic patients with WE is presented and an assessment is made on whether a delay in diagnosis leads to a worse prognosis. PATIENTS AND METHODS: The clinical records of patients admitted to 2 university hospitals between 2004 and 2009 with the diagnosis of WE, excluding those with a history of alcoholism, were retrospectively reviewed. RESULTS: The study included 4 men and 4 women aged 35-82 of whom 7 had a history of gastrointestinal pathology, and persistent vomiting was the precipitating factor in 7. Encephalopathy was the most frequent onset symptom (4). The classical triad was present in seven patients. Thiamine levels were low in 3/6 and normal in 3/6 cases. MRI was abnormal in seven patients, with high signal intensity in the diencephalon and mammillary bodies (7), periaqueductal grey matter (6), cortex (3) and cerebellum (1). Seven improved with thiamine. Sequelae were mild in 6, and severe in 2 after 6-12 months of follow-up. All patients with a diagnostic delay less than 18 days had mild sequelae. CONCLUSIONS: Non-alcoholic WE frequently occurs after gastrointestinal disturbances that could result in lower thiamine absorption. Whereas thiamine levels can be normal in many cases, in almost all cases the MRI shows signal alterations in typical locations. A delay in the diagnosis, and therefore, in treatment leads to a worse prognosis.

Pelvic dyskinesia with an outstanding response to tetrabenazine.

We report on a patient who presented an invalidating progressive pelvic dyskinesia while receiving different kinds of neuroleptic drugs for a psychiatric disorder. The clinical features and different drug-induced movement scales showed an outstanding improvement after tetrabenazine was started. To the best of our knowledge, this is the first case report of pelvic dyskinesia with good evolution and control of dyskinesias after treatment with tetrabenazine.

Familial Creutzfeldt-Jakob disease with E200K mutation presenting with neurosensorial hypoacusis.

Creutzfeldt-Jakob disease (CJD) is characterised by rapidly progressive dementia, myoclonus, ataxia, visual disturbances and motor dysfunction. Most of the cases are sporadic. Only 10% to 15% are familial, and the most frequent point mutation is E200K. A 53-year-old man presented with subacute progressive bilateral hypoacusis, with tinnitus in the left ear. During the following months, his hypoacusis worsened and he progressively developed bilateral stocking-type paresthaesia and gait instability. An audiometric examination showed bilateral neurosensorial hypoacusis and nerve conduction studies showed a mixed axonal polyneuropathy. A CT scan and MRI of the brain were normal and the electroencephalography (EEG) showed non-specific changes. He died of respiratory infection 10 months after onset of symptoms. Neuropathological examination showed neuronal loss, punctate, synaptic-like deposits of protease-resistant prionic protein (PrP(RES)) in the cerebral and cerebellar cortices and auditory nuclei. This is a rare case of sporadic CJD presenting with hearing loss.

[Frontotemporal lobar degeneration: a descriptive study of 42 patients]. / Degeneración lobular frontotemporal: estudio descriptivo de 42 pacientes.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is considered to be the second cause of presenile dementia. In spite of the great interest it has generated over the last few years, few studies have been published in our country. METHODS: A descriptive retrospective study of 42 patients with FTLD evaluated in our unit during the period 1996-2006 was performed. RESULTS: Thirty one patients presented with frontal variant FTLD (FTD), eigth with non-fluent progressive aphasia and three with semantic dementia. Mean age at onset was 56 years, diagnostic delay 3.5 years and mean survival 6.8 years. 35% had a family history suggestive of dementia. In patients with FTD the clinical expression was a combination of behavioral and personality disorders together with language impairment. Magnetic resonance imaging showed frontal and/or temporal atrophy in 62% of cases and SPECT showed frontal and/or temporal hypoperfusion in 75%. The P301L tau mutation was detected in four patients (two of them siblings) and the A303AfsX57 progranulin mutation in one. Necropsy was performed in five patients, revealing FTLD with ubiquitininmunoreactive inclusions (FTLD-U) and motor neuron disease in two cases, FTLD-U with <> shaped intranuclear inclusions in the case with the progranulin mutation and FTLD tauopathy with predominance of 4R tau in the remaining two, both with the P301L mutation. CONCLUSIONS: Our results are similar to those of the great European series. FTLD must be suspected in presenile patients with prominent behavioral and/or language disorders. Neuroimaging supports the diagnosis in the majority of cases. The huge sociofamiliar impact of FTLD, presenile onset, high frequency of familial history of dementia and possibility of genetic study and counseling highlight its clinical relevance.

Increased cerebral activity in Parkinson's disease patients carrying the DRD2 TaqIA A1 allele during a demanding motor task: a compensatory mechanism?

Previous studies suggest that neuroimaging techniques are useful for detecting the effects of functional genetic polymorphisms on brain function in healthy subjects or in patients presenting with psychiatric or neurodegenerative conditions. Former evidence showed that individuals carrying risk alleles displayed broader patterns of brain activity during behavioural and cognitive tasks, despite being clinically comparable to non-carriers. This suggests the presence of compensatory brain mechanisms. In the present study, we investigated this effect in Parkinson's disease (PD) patients carrying the DRD2 TaqIA A1 allelic variant. This variant may confer an increased risk of developing the disease and/or influence the clinical presentation. During a complex sequential motor task, we evidenced by functional magnetic resonance imaging that A1 allele carriers activated a larger network of bilateral cerebral areas than non-carriers, including cerebellar and premotor regions. Both groups had similar clinical and demographic measures. In addition, their motor performance during the functional magnetic resonance experiment was comparable. Therefore, our conclusions, pending replication in a larger sample, seem to reflect the recruitment of compensatory cerebral resources during motor processing in PD patients carrying the A1 allele.

[A pilot study on a specific measure for sleep disorders in Parkinson's disease: SCOPA-Sleep]. / Estudio piloto sobre una medida especifica para los trastornos del sueno de la enfermedad de Parkinson: SCOPA-sueño.

INTRODUCTION: There is a high prevalence of sleep disorders in Parkinson's disease (PD). AIMS. To assess some basic metric attributes of the SCOPA-Sleep scale, a measure for PD patients; secondary objective: to check the impact caused by the sleep disorder on the health-related quality of life (HRQoL) of patients and their caregivers. SUBJECTS AND METHODS: 68 PD patients and their main caregivers; measures: Hoehn and Yahr staging, SCOPA-Motor, Clinical Impression of Severity Index (CISI-PD), PDSS, Hospital Anxiety and Depression Scale, SCOPA-Psychosocial, and EuroQoL. Carers filled in a PDSS questionnaire about patient sleep and HRQoL measures (SF-36, EuroQoL). SCOPA-Sleep acceptability, scaling assumptions, internal consistency, construct validity and precision were determined. RESULTS: SCOPA-Sleep acceptability and scaling assumptions resulted satisfactory, although the nocturnal sleep subescale (SC-Ns) showed a mild ceiling effect (22.1%) and a defective convergent validity was found for daytime sleepiness (SC-Ds) item 6. Internal consistency also was satisfactory for both scales (alpha = 0.84 and 0.75, respectively). The correlation between SC-Ns and PDSS was high (rs = -0.70), as it was between SC-Ns and PDSS questionnaire by caregiver (rs = -0.53). The corresponding coefficients with the SC-Ds gained lower values (rs = -0.41 y -0.50). Standard error of measurement was 1.45 for the SC-Ns and 1.76 for the SC-Ds. Both, patient and caregiver HRQoL showed a loose association with the sleep measures. CONCLUSION: SCOPA-Sleep is a feasible, consistent, and useful scale for assessment of sleep disorder in PD patients. A weak association between sleep disorder and HRQoL was found.

Sequence analysis of tau 3'untranslated region and saitohin gene in sporadic progressive supranuclear palsy.

BACKGROUND: The extended tau H1 haplotype has previously been described in association with progressive supranuclear palsy (PSP). Recently, a new gene called saitohin (STH), nested within an intron of tau, has been discovered. The Q7R polymorphism of STH appears to be related to late onset Alzheimer's disease. OBJECTIVES: To search for genetic changes in the 3'untranslated region (3'UTR) of tau and adjacent sequence LOC147077, and in the coding region of STH in PSP patients. METHODS: The study included 57 PSP patients and 83 healthy controls. The genetic analysis of each region was performed through sequencing. The Q7R polymorphism was studied through restriction enzyme and electrophoresis analysis. RESULTS: No mutations were found in the regions analysed. The QQ genotype of the STH polymorphism was over-represented in participants with PSP (91.5%) compared with control subjects (47%) (p< or =0.00001). This genotype co-segregated with the H1/H1 haplotype in our PSP cases. CONCLUSIONS: Our results do not support a major role for the tau 3'UTR in PSP genetics. The QQ genotype of STH confers susceptibility for PSP and is in linkage disequilibrium with the H1/H1 haplotype.

[Cerebrotendinous xanthomatosis without tendinous xanthomas: presentation of two cases]. / Xantomatosis cerebrotendinosa sin xantomas tendinosos: presentación de dos casos.

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder caused by a 27-hydroxilase enzyme deficiency, leading to beta-cholestanol storage in many body tissues. Clinically, the disease is characterised by the presence of tendinous xanthomas, juvenile cataracts and progressive neurologic dysfunction. The diagnosis requires beta-cholestanol quantification in serum. We report two siblings with a history of photosensitive epilepsy of childhood onset, who developed progressive spastic paraparesis and cataracts in their third decade of life. They were diagnosed to have CTX in spite of the absence of tendinous xanthomas. Cranial and spinal MRI only showed bilateral high intensity signal in the dentate nuclei in the T2-weighted and proton-density sequences. Our patients presented with a progressive spastic paraparesis. The delay in the diagnosis in our case could be due to the absence of tendinous xanthomas and late-onset cataracts. The recognition of the disease is important, because the treatment with chenodeoxycholic acid induces a decrement of beta-cholestanol levels in serum and could prevent the progression of the disease.

Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism.

BACKGROUND: Autosomal recessive juvenile parkinsonism is a neurodegenerative disorder associated with mutations in the parkin gene. OBJECTIVES: To search for the presence of parkin gene mutations in Spanish patients with Parkinson's disease (PD) and characterise the phenotype associated with these mutations. METHODS: Thirty seven PD patients with either early onset or autosomal recessive pattern of inheritance were selected for genetic study. RESULTS: Mutations were identified in seven index patients (19%). Homozygous mutations were detected in six patients and a heterozygous mutation in one. The age at onset was lower in patients with mutations than in patients without mutations. Dystonia at onset was present in two patients with parkin gene mutations. The disease began in two patients with postural tremor in the upper limbs mimicking essential tremor. Four patients exhibited a long term response to dopamine agonists. The c.255delA mutation was identified in four unrelated families. This is a frameshift mutation leading to protein truncation. CONCLUSIONS: Parkin gene mutations are present in Spanish patients with early onset and/or an autosomal recessive parkinsonism. The c.255delA is the most frequent mutation found, suggesting a relative high prevalence in the Spanish population.

[Antithrombotic treatment of fusiform aneurysms of the basilar artery]. / Tratamiento antitrombótico en los aneurismas fusiformes de la arteria basilar.

Fusiform aneurysms are unusual, and they are most found in the vertebrobasilar system. Although the presence of such aneurysms has been related to atheromatous degeneration of the arterial wall, in many cases the cause of their formation is unknown. The clinical manifestations of fusiform aneurysms of the vertebrobasilar system are generally due to mass effect with compression of adjacent structures or to ischemic events; exceptionally they are due to subarachnoidal haemorrhage. We present the case of a patient with symptoms suggestive of brainstem ischemic damage, in which neuroimaging showed a fusiform aneurysm of the basilar artery with an intraaneurysmatic thrombus. Antiaggregation did not prevent new ischemic events, so anticoagulation therapy was initiated. The patient remained asymptomatic at 8 months of follow-up. The treatment of fusiform aneurysms is controversial; however, there are some evidences in the literature supporting that patients with ischemic events may be treated with long term anticoagulation, especially in cases of non-giant aneurysms of the vertebrobasilar system not accompanied by aneurysms in other sites.

Splenectomy for refractory Evans' syndrome associated with antiphospholipid antibodies: report of two cases.

The main haematological manifestations seen in patients with antiphospholipid antibodies (aPL) are thrombocytopenia, usually mild, and haemolytic anaemia with a positive Coombs test. Owing to the shared characteristics with idiopathic thrombocytopenic purpura, similar rules are followed in the treatment of these cytopenias. Two patients with severe aPL associated cytopenias, who required splenectomy after being refractory to steroids, immunosuppressive agents, and other treatments (intravenous gammaglobulin, danazol), are described, and previously reported cases are reviewed.