Long-term effects of cognitive rehabilitation on brain, functional outcome and cognition in Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive rehabilitation has demonstrated efficacy in producing short-term cognitive and brain changes in patients with Parkinson's disease (PD). To date, no study has assessed the long-term effects of cognitive rehabilitation using neuroimaging techniques in PD. The aim was to assess the longitudinal effects of a 3-month cognitive rehabilitation programme evaluating the cognitive, behavioural and neuroimaging changes after 18 months. METHODS: Fifteen patients with PD underwent a cognitive, behavioural and neuroimaging assessment at pre-treatment (T0 ), post-treatment (T1 ) and after 18 months (T2 ). This study examined the long-term effects (from T0 to T2 ) and the maintenance of the changes (from T1 to T2 ). T1-weighted, diffusion-weighted, functional magnetic resonance imaging during both a resting-state and a memory paradigm were acquired. Voxel-based morphometry and tract-based spatial statistics were used for grey and white matter analyses. A region-of-interest-to-region-of-interest approach was used for resting-state functional connectivity (FC) and a model-based approach was used for brain activation during the memory paradigm. RESULTS: Patients with PD showed increased cognitive performance, decreased functional disability, increased brain FC and activation at T2 compared with T0 (P < 0.05, FDR). Moreover, patients showed maintenance of the improvements in cognition and functionality, and maintenance of the increased brain FC and activation at T2 compared with T1 . However, significant grey matter reduction and alterations of white matter integrity were found at T2 (P < 0.05, FWE). CONCLUSIONS: Findings suggest that the improved cognitive performance and increased brain FC and activation after cognitive rehabilitation were significantly maintained after 18 months in patients with PD, despite the structural brain changes, consistent with a progression of neurodegenerative processes.

Progression from amnesic mild cognitive impairment to Alzheimer's disease: ESR1 and ESR2 polymorphisms and APOE gene.

BACKGROUND: Many genes have been studied to determine how they might be involved in Alzheimer's disease (AD). Estrogens have a protective effect in the central nervous system. The mechanisms of action of estrogens are mediated by two estrogen receptors (ERs), ERα and ERß. Thus, these genes could also play a role in the progression of amnesic mild cognitive impairment (MCIa) to AD. The aim of this study was to examine the role of ER single nucleotide polymorphisms (SNPs) as a risk factor for MCIa, as well as the interaction with apolipoprotein E (APOE) ε4 in the progression to AD. METHODS: 79 MCIa patients and 138 healthy controls were analyzed. SNPs were genotyped via restriction fragment length polymorphisms and real-time PCR, RT-PCR or RT-PCR (TaqMan) assays. RESULTS: There is a lack of association between MCIa patients who converted to AD and ER SNPs. APOE ε4 allele is an independent risk factor of MCIa (OR=1.86; 95% CI=1.02-3.38, p=0.042) with a high prevalence in converted subjects. APOE ε4 is able to predict the progression from MCIa patients to AD (OR=2.55; 95% CI=1.20-5.42, p=0.015). CONCLUSIONS: The presence of the APOE ε4 allele, and not the alleles of ER SNPs, is a risk factor for MCIa. Furthermore, APOE genotype seems to predict the conversion from MCIa to AD.

[Reversible alterations in the dentate nuclei and rapid-onset cerebral atrophy due to neurotoxicity caused by lithium]. / Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.

INTRODUCTION: Treatment with lithium can cause several neurological side effects, even at therapeutic levels. CASE REPORT: We report the case of a 49-year-old woman, with bipolar disorder and depression, undergoing treatment with lithium, antidepressants and antipsychotics, who was admitted to hospital due to a clinical picture of visual hallucinations with an elevated lithaemia of 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). The patient developed a severe encephalopathy that required the use of assisted ventilation in the intensive care unit. Initial magnetic resonance imaging showed a reversible bilateral symmetrical hyperintensity in the dentate nuclei in T2 and T2-FLAIR sequences. Over the following months she gradually developed a pancerebellar syndrome with evidence of a marked loss of bilateral volume in the cerebellum, above all at the expense of the vermis, which was accompanied by a permanent and disabling cerebellar syndrome. CONCLUSIONS: Although treatment with lithium can cause a variety of neurological side effects, they are usually reversible. However, they occasionally give rise to permanent and disabling sequelae, as in the case of the patient reported here, with a marked and progressive cerebellar atrophy, accompanied by permanent sequelae in the form of a disabling cerebellar syndrome. The cerebellar neurotoxicity of lithium must be taken into account in the broad differential diagnosis of cerebellar ataxia in adults.

TITLE: Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.Introduccion. El tratamiento con litio puede ocasionar diversos efectos adversos neurologicos, incluso con niveles terapeuticos. Caso clinico. Mujer de 49 años, con trastorno bipolar y depresion, en tratamiento con litio, antidepresivos y antipsicoticos, que ingreso por un cuadro de alucinaciones visuales con una litemia elevada de 2,1 mEq/L (rango terapeutico: 0,6-1,2 mEq/L). Progreso a una encefalopatia grave que requirio asistencia respiratoria en la unidad de cuidados intensivos. La resonancia magnetica cerebral inicial mostro una hiperintensidad simetrica bilateral reversible en los nucleos dentados en las secuencias T2 y T2-FLAIR. A lo largo de los meses posteriores desarrollo de forma progresiva un sindrome pancerebeloso con evidencia de una marcada perdida de volumen bilateral en el cerebelo, sobre todo a expensas del vermis, que se acompaño clinicamente de un sindrome cerebeloso permanente e invalidante. Conclusiones. Aunque el tratamiento con litio ocasiona efectos adversos neurologicos variados, estos suelen ser reversibles. Puede dar lugar a secuelas permanentes e incapacitantes, como la paciente descrita, con una atrofia cerebelosa marcada y progresiva, acompañada de secuelas permanentes en forma de sindrome cerebeloso invalidante. La neurotoxicidad cerebelosa del litio debe considerarse en el amplio diagnostico diferencial que representa la ataxia cerebelosa del adulto.

Resolution of a brainstem abscess through antituberculous therapy.

We describe an immunocompetent patient with a solitary brainstem abscess that responded to antituberculous therapy. Although prompt surgical therapy has been advocated, the possibility of medical resolution of brainstem tuberculous abscesses should be considered.

Procedural learning is impaired in patients with prefrontal lesions.

OBJECTIVES: To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. BACKGROUND: Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack of studies examining patients with prefrontal cortex lesions. METHODS: We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. RESULTS: Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. CONCLUSIONS: The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning.

[Multifocal motor neuropathy after administration of gangliosides]. / Neuropatía motora multifocal tras la administración de gangliósidos.

A case of a 38 years-old male with motor neuropathy with multifocal conduction blocks following the administration of ganglioside therapy is reported. There was generalized weakness without areflexia and normal parameters of the spinal fluid, including protein values. Electrophysiological data showed multiple conduction blocks with normal nerve conduction velocities. Antibodies against asialo-GM1 gangliosides were present in the cerebrospinal fluid. There could be a relationship between the ganglioside administration and the development of an immune-mediated neuropathy. Several cases of demyelinating polyradiculoneuritis after ganglioside treatment have been reported. If this association is confirmed, the apparent lack of toxicity of gangliosides should be reconsidered.

[Personality factors, degree of disability and therapeutic management of patients with migraine visiting a neurology unit for the first time (Psicomig study)]. / Factores de personalidad, grado de discapacidad y abordaje terapeutico de los pacientes con migrana atendidos en primera consulta en neurologia (estudio Psicomig).

INTRODUCTION: Migraine has recently been associated to certain personality profiles and styles of coping. AIM: To explore the association between personality factors, disability and the therapeutic management of migraine. PATIENTS AND METHODS: We conducted an epidemiological, cross-sectional, multi-centre study with patients with migraine visiting a neurology unit for the first time. Socio-demographic and clinical data were collected about the patients. The NEO-FFI (Neuroticism-Extraversion-Openness Five-Factor Inventory) was used to evaluate personality factors; the degree of disability was evaluated using the Headache Impact Test (HIT-6) and the number of lost workday equivalents (LWDE) was measured. Bivariate logistic regression analyses were also performed. RESULTS: A total of 736 patients were recruited, of whom 700 were suitable for inclusion in the analysis (75.6% females; mean age: 35.5 ± 11.5 years). In all, 68.9% presented migraine without aura, 1-4 seizures/month (66.7%) and of moderate intensity (58.1%). A total of 76.1% of patients had severe disability according to the HIT-6. Of the 554 active patients, the mean number of lost workday equivalents in the previous three months was 6.8 ± 8.2. Patients showed greater emotional instability than the general population and they scored lower on extraversion, openness, agreeableness and conscientiousness. All the patients were being treated for their migraine: 47.3% by means of stepped treatment between seizures; 39.9% intra-seizures, and stratified in only 12.9%. CONCLUSIONS: This study confirms the impact of migraine in terms of disability and in terms of loss of labour output, together with its association with personality factors.

Impact of preventive therapy with nadolol and topiramate on the quality of life of migraine patients.

Preventive therapy is aimed at reducing migraine frequency, but should also improve the much deteriorated quality of life of the migraneur. We aimed to evaluate the impact of preventive therapy with two widely employed drugs (topiramate and nadolol) on the quality of life of migraine patients. A population of consecutive migraineurs aged > or = 16 years, with frequent migraines, was selected prospectively for evaluation at baseline and after 16 weeks of therapy with nadolol or topiramate (40 mg and 100 mg daily, respectively) by generic and specific quality of life questionnaires (SF-36 and MSQOL) and by an anxiety and depression scale (HADS). Preventive therapy resulted in a statistically significant improvement in physical domains of the SF-36, whereas mental domains remained almost unchanged. Despite this improvement, all domains remained below the population norms. The HADS revealed a moderate depressive state at baseline that did not change with therapy. The MSQOL global score also revealed statistically significant improvement. Both drugs were similarly effective, although topiramate was superior on the role physical domain compared with nadolol. Preventive therapy with nadolol and topiramate significantly improves the quality of life of migraineurs, although additional efforts are needed to place them in a nearer-to-normal situation compared with the general population.

[Cannabis and cerebrovascular disease]. / Cannabis y patología vascular cerebral.

INTRODUCTION: Drug use is a well-kown risk factor for cerebrovascular disease in young people. Cannabis is the most widely consumed among the illicit drugs worldwide, but it has only exceptionally been associated to cerebrovascular disease. CLINICAL CASE: We here describe 2 young patients (26 and 29 years, respectively) who suffered from ischemic stroke in temporal relation with cannabis consumption. CONCLUSIONS: The review of the literature on this topic reveals another 18 patients with stroke in association to cannabis use. They all were young people with ischemic stroke. Although a causal relationship is difficult to establish due to the widespread use of cannabis, this drug may play an etiologic role in ischemic stroke.

Recurrent stroke associated with cannabis use.

Drug misuse represents a risk factor for cerebrovascular disease, especially among young people. Despite the fact that cannabis is the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular disease. We describe a patient who suffered three ischaemic strokes immediately after cannabis consumption. Other stroke aetiologies were ruled out, and neuroimaging revealed infarcts in different arterial areas as well as evidence of non-atherosclerotic arterial disease, which suggests an underlying vasculopathy of uncertain (toxic or inflammatory) origin. Cannabis use may be associated with ischaemic stroke in young patients, but its mechanism is unclear.

[Acute confusional state secondary to transient headache and neurological deficits with cerebrospinal fluid lymphocytosis]. / Estado confusional agudo secundario a síndrome de cefalea y déficit neurológicos transitorios con linfocitosis en líquido cefalorraquídeo.

Pseudomigraine with pleocytosis (now referred to as syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis, IHS ICHD-II code 7.8) is only infrequently accompanied by a confusional state and no cases have been described so far in association with severe agitation. We report on a patient who suffered from two episodes of headache with transient focal neurological deficits that were consistent with pseudomigraine with pleocytosis but that were followed by an intense confusional, agitated state that required admission in the intensive care unit. This possibility should be included in the differential diagnosis of confusional, agitated states.

Bilateral vertebral artery dissection in a patient with afibrinogenemia.

BACKGROUND: Afibrinogenemia, a rare coagulation disorder, has not been associated with vertebral artery dissections. CASE DESCRIPTION: A 28-year-old woman with afibrinogenemia developed spontaneous neck pain followed by a right medullary infarction, and MR angiography showed extensive bilateral vertebral artery dissection. She was treated with fibrinogen replacement and anticoagulants and showed a favorable evolution, with only mild residual right upper arm incoordination. CONCLUSIONS: In this patient spontaneous bilateral vertebral artery dissection complicated afibrinogenemia. Since anticoagulant therapy is usually indicated for arterial dissection, this association created a therapeutic problem. This patient received anticoagulants with fibrinogen replacement, which resulted in a favorable evolution.

Hypoglossal schwannoma: an uncommon cause of twelfth-nerve palsy.

Hypoglossal schwannoma is an uncommon cause of 12th nerve palsy. We here report a pathologically proven case of left 12th nerve schwannoma in a 56-year-old woman who presented with progressive left tongue hemiatrophy and in whom cranial MRI disclosed a mass near the foramen jugular. Surgery showed a mass involving the hypoglossal nerve and the pathological examination was diagnostic of schwannoma.