Luísa Alves

Alzheimer's disease: a clinical practice-oriented review

Investigation in the field of Alzheimer’s disease (AD), the commonest cause of dementia, has been very active in recent years and it may be difficult for the clinician to keep up with all the innovations and to be aware of the implications they have in clinical practice. The authors, thus, reviewed recent literature on the theme in order to provide the clinician with an updated overview, intended to support decision-making on aspects of diagnosis and management. This article begins to focus on the concept of AD and on its pathogenesis. Afterward, epidemiology and non-genetic risk factors are approached. Genetics, including genetic risk factors and guidelines for genetic testing, are mentioned next. Recommendations for diagnosis of AD, including recently proposed criteria, are then reviewed. Data on the variants of AD is presented. First approach to the patient is dealt with next, followed by neuropsychological evaluation. Biomarkers, namely magnetic resonance imaging, single photon emission tomography, FDG PET, PiB PET, CSF tau, and Aβ analysis, as well as available data on their diagnostic accuracy, are also discussed. Factors predicting rate of disease progression are briefly mentioned. Finally, non-pharmacological and pharmacological treatments, including established and emerging drugs, are addressed.

Normal-pressure hydrocephalus: White matter lesions correlate negatively with gait improvement after lumbar puncture

OBJECTIVES To test relations between white matter lesions (WML) load in Normal Pressure Hydrocephalus (NPH) patients and gait characteristics at baseline, duration of symptoms, gait improvement after lumbar puncture (LP), vascular risk factors. PATIENTS Fifteen idiopathic NPH patients. METHODS Patients underwent a timed walking test, before and after LP. Five gait variables were assessed and improvement percentages were calculated. WML load was rated regionally and globally in T2 weighted MRI images, using a simple visual scale. Spearman or Pearson correlation coefficients were used to test relations between variables. RESULTS Significant negative correlations were found between WML scores and gait improvement after CSF removal but not with duration of symptoms or gait variables before LP. CONCLUSIONS WML seem to contribute to the irreversibility of symptoms in NPH but not to the pathophysiological mechanisms that lead to them.

Profile of cognitive dysfunction and relation with gait disturbance in Normal Pressure Hydrocephalus

OBJECTIVES Although dementia is one of the most relevant symptoms of the idiopathic Normal-Pressure Hydrocephalus (iNPH) syndrome, some doubts remain about the nature of cognitive deficits in this disease. We aimed to determine the neuropsychological profile in iNPH and its relation with ventricular size, white matter vascular lesions (WML) and gait dysfunction. METHODS Seventeen iNPH patients and a control group (n=14) were assessed with a battery of neuropsychological tests and a timed walk test. We calculated measures of frontal horn, occipital horn and third ventricle sizes and assessed white matter lesion (WML) load with a validated visual scale. RESULTS Patients differed significantly from controls in all cognitive tests, but did worse on the Rey Complex Figure test. We found no significant correlations between cognitive and imaging results in iNPH. Cognitive function was related to gait in controls, but not in iNPH patients. CONCLUSIONS Patients presented widespread cognitive dysfunction with a predominance of visuo-spatial deficits. Dissociation between gait and cognitive dysfunction in iNPH patients suggests the existence of different pathophysiological mechanisms.

Normal pressure hydrocephalus: a qualitative study on outcome

OBJECTIVE To describe the natural history and shunt outcome in patients with normal pressure hydrocephalus (NPH) and the variables that influence both. METHOD Motor and cognitive parameters of 35 patients with NPH, as well as shunt surgery status, were registered at two time points (T0 and T1). RESULTS Thirteen patients underwent shunt surgery. Favorable outcome in gait function occurred in 5 of 35 patients and was related to younger age, absence of cardiovascular risk factors (CVRF) and white matter lesions (WML), and shunt surgery. Cognitive outcome was favorable in 9 of 35 patients and associated with shunt surgery (trend level). Of the patients subjected to surgery, favorable outcome in motor function was related to younger age at T0 and absence of CVRF and WML (trend level). CONCLUSION Shunt surgery had a significant effect on gait and less on cognition. Favorable outcome in gait was also associated with younger age and absence of CVRF and WML.

Teaching Video NeuroImages: Candy sign The clue to the diagnosis of neurosyphilis

A 45-year-old man presented with rapid progressive cognitive decline and behavioral symptoms. Neurologic examination revealed global cognitive impairment and episodic, nonrhythmic, brief contractions of the left orofacial muscles (video at Neurology.org). Serologic tests for syphilis were positive without HIV coinfection. CSF analysis revealed cell count 15/μL (mononuclear), hyperproteinorrachia (100 mg/dL), normal glycorrachia, intrathecal immunoglobulin G synthesis (index-3.09), oligoclonal bands (type 2), and venereal disease research laboratory titer of 1/4. MRI revealed bilateral nonspecific white matter changes. Although rare and seldom documented, this dyskinesia, coined candy sign, is considered pathognomonic of neurosyphilis.1 Improvement with penicillin was observed, but response to treatment seems to be variable.2