RESUMO
Epileptic seizure is the common symptom associated with lipomas in the Sylvian fissure (Sylvian lipomas). Removal of these lipomas carries risks of hemorrhage and brain damage. We report a surgical strategy of not removing the lipoma in a case of intractable temporal lobe epilepsy associated with Sylvian lipoma. We performed anterior temporal lobectomy with preservation of the pia mater of the Sylvian fissure and achieved seizure freedom. Focal cortical dysplasia type 1 of the epileptic neocortex adjacent to the Sylvian lipoma was pathologically diagnosed. We recommend our surgical procedure in similar cases to avoid complications and achieve adequate seizure control.
Assuntos
Neoplasias Encefálicas , Epilepsia do Lobo Temporal , Epilepsia , Lipoma , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/cirurgia , Imageamento por Ressonância Magnética/efeitos adversos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Convulsões , Lipoma/complicações , Lipoma/diagnóstico por imagem , Lipoma/cirurgiaRESUMO
The design and synthesis of a novel class of 7-azaspiro[3.5]nonane GPR119 agonists are described. In this series, optimization of the right piperidine N-capping group (R2) and the left aryl group (R3) led to the identification of compound 54g as a potent GPR119 agonist. Compound 54g showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose lowering effect in diabetic rats.
Assuntos
Alcanos/química , Desenho de Fármacos , Receptores Acoplados a Proteínas G/agonistas , Alcanos/síntese química , Alcanos/farmacocinética , Animais , Glicemia/análise , Linhagem Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Teste de Tolerância a Glucose , Meia-Vida , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Microssomos Hepáticos/metabolismo , Piperidinas/química , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-AtividadeRESUMO
Patients with Parkinson's disease (PD) experience significantly reduced quality of life when PD is complicated with Pisa syndrome (PS). PS is a postural abnormality associated with a lateral bending of the trunk, causing the patient to lean to one side. Microsaccades during fixation are transmitted to the visual cortex, and this gaze movement may be impaired in PD. We aimed to detect presymptomatic signs of PS. We enrolled 50 patients with PD without dementia and investigated the visual systems in patients with concurrent PD and PS based on a Romberg ratio of<1.0. Gaze analysis, pupil diameter, stabilization tests, neuropsychological tests, and cerebral perfusion scintigraphy were reviewed and statistically analyzed. Two years later, we divided the patients into three groups as follows: PISA++ (patients who had PS at enrollment), PISA-+ (patients without PS that developed PS during the 2-year period), and PISA-- (patients without PS that did not develop PS during the 2-year period). The PISA-+ group exhibited a significantly higher daily levodopa dose and longer fixations, as well as lower position discrimination, Wechsler Adult Intelligence Scale-Third Edition blocking, and blood flow in the left supramarginal and orbital gyri than that in the PISA-- group. The PISA++ group showed a significantly longer fixation time and lower Mini-Mental State Examination score, Romberg ratio of area, amplitude, velocity of microsaccades, and blood flow in the left precuneus and cuneus than that in the PISA-+ group. Before the onset of PS, hypoperfusion occurred in the correlative visual cortex and the position discrimination test. Patients with PS have reduced saccades and slow microsaccades.
RESUMO
Objective: It is difficult to distinguish patients with schizophrenia with neuroleptic-induced parkinsonism (NIP) from those with existing idiopathic Parkinson's disease when their striatal dopamine transporter uptake is reduced. There is a possibility of misdiagnosis of Parkinson's disease in patients with schizophrenia as schizophrenia with NIP, which leads to inappropriate treatment. This prospective study aimed at determining the underlying pathophysiology using detailed clinical and psychological assessments. Methods: We enrolled six patients with schizophrenia who had parkinsonism and were diagnosed with Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria, except for the fifth absolute exclusion criteria. Results: Five patients had been treated with neuroleptics for 20 years. One patient refused treatment for schizophrenia. All patients had impaired cognitive function at enrolment, olfactory dysfunction, and constipation. All patients were treated with dopaminergic therapy, and their parkinsonism substantially improved; one woman in her 40s experienced a wearing-off effect and dyskinesia. The uptake of dopamine transporter in the striatum decreased by 13%/year during the study period. Conclusion: Some patients with schizophrenia and parkinsonism benefit from dopaminergic therapy. Some of these patients may also exhibit Lewy pathology.
RESUMO
Temporal lobe epilepsy with amygdala enlargement (TLE-AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE-AE, who underwent intracranial video-EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Eleven patients with TLE-AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale-Revised (WMS-R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. The mean age at seizure onset was 34.9 years (range: 23-57). The mean duration of seizures was 5.0 years (range: 1-10). The number of AEDs was 2.3 (range: 1-5). The mean seizure frequency was nine per month (range: 1-30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p<0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre-operative mean verbal, visual, and delayed recall scores based on the WMS-R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non-dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow-up of 26 months (range: 12-47). Post-operative WMS-R results did not show any significant deterioration, with a mean follow-up of 15 months (range: 12-24). The resected amygdala showed no histopathological abnormality. The epileptogenic zone of TLE-AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE-AE.
Assuntos
Tonsila do Cerebelo/patologia , Epilepsia Resistente a Medicamentos/patologia , Eletrocorticografia , Hipocampo/patologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Lobectomia Temporal Anterior/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Lobo Temporal/fisiopatologiaRESUMO
BACKGROUND: Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. OBJECTIVE: To investigate whether LPSs, including gravitational "add-on" and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. METHODS: We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. RESULTS: Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. CONCLUSION: This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.
Assuntos
Catéteres , Derivações do Líquido Cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Abdome/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Gravitação , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is commonly treated by cerebrospinal fluid (CSF) shunting. However, the long-term efficacy of shunt intervention in the presence of comorbid Alzheimer's disease (AD) pathology is debated. OBJECTIVE: To identify AD-associated CSF biomarkers predictive of shunting surgery outcomes in patients with iNPH. METHODS: Preoperative levels of total and phosphorylated Tau (p-Tau) were measured in 40 patients with iNPH divided into low (<30 pg/mL) and high (≥30 pg/mL) p-Tau groups and followed up for three years after lumboperitoneal shunting. The modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and iNPH Grading Scale scores were compared between the age-adjusted low (nâ=â24; mean age 75.7 years [SD 5.3]) and high (nâ=â11; mean age 76.0 years [SD 5.6]) p-Tau groups. RESULTS: Cognitive function improved early in the low p-Tau group and was maintained thereafter (pâ=â0.005). In contrast, the high p-Tau group showed a gradual decline to baseline levels by the third postoperative year (pâ=â0.040). Although the p-Tau concentration did not correlate with the preoperative MMSE score, a negative correlation appeared and strengthened during follow-up (R2â=â0.352, pâ<â0.001). Furthermore, the low p-Tau group showed rapid and sustained mRS grade improvement, whereas mRS performance gradually declined in the high p-Tau group. CONCLUSIONS: Preoperative CSF p-Tau concentration predicted some aspects of cognitive function after shunt intervention in patients with iNPH. The therapeutic effects of shunt treatment were shorter-lasting in patients with coexisting AD pathology.
Assuntos
Cognição/fisiologia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Cuidados Pré-Operatórios/métodos , Derivação Ventriculoperitoneal/tendências , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia de Pressão Normal/psicologia , Masculino , Pessoa de Meia-Idade , Fosforilação/fisiologia , Prognóstico , Fatores de TempoRESUMO
The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPPα, sAPPß), amyloid ß (Aß)1-38, Aß1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/ß-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), Aß1-38/Aß1-42 ratio (77.8%, 81%, 3.58), and the Aß1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from Aß1-42 to Aß1-38.
Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas Amiloidogênicas/líquido cefalorraquidiano , Transtornos Cognitivos , Cistatina C/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/complicações , Oxirredutases Intramoleculares/líquido cefalorraquidiano , Lipocalinas/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Derivações do Líquido Cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Feminino , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
We report on 8 patients with Parkinson's disease (PD) who experienced suddenly episodes of speech unrelated to the topic of conversation or wrote sentences unrelated to the context. During these episodes and later, unless pointed out, patients were unaware of the behavior. We called this phenomenon Unrelated Communication Interlude (UCI). All patients were male; half of them with impulse control disorders (punding, hypersexuality, or pathological gambling). Four patients reported sleepiness when the episodes of UCI occurred. There were no significant differences in age at examination, age of onset of PD, and neuropsychological tests score (Mini-Mental State Examination, Frontal Assessment Battery, and Beck Depression Inventory) between patients with UCI and those without. To our knowledge, this is the first reported phenomena of such abnormal behavior in Parkinson's disease. UCI was considered as automatic behavior similar to that seen in narcolepsy and excessive daytime sleepiness. UCI might be occurring in relation to excessive daytime sleepiness in PD.