[Introduction of a brief Problem-Based-Learning (PBL) experience in traditional medical faculty curriculum].

BACKGROUND: For medical students studying in a traditional medical curriculum, advancement from the pre-clinical years to clinical clerkships requires a conceptual move from disease-oriented thinking to problem-oriented medicine. OBJECTIVE: To implement an educational tool in the introductory course of clinical medicine that will assist students in the development of comprehensive medical reasoning, including the generation of a dynamic problem list, its assessment and the construction of investigative and treatment plans. METHODS: Since 2001 a novel brief Problem-Based Learning (PBL) experience has been offered as a component of the Introduction to Medicine course given to 4th year medical students prior to the start of their clinical years at the Hebrew University Medical School. The brief experience consists of daily meetings given to small groups of students at the final stages of the pre-clinical courses. Each PBL day covers a single clinical case revealed sequentially over 3-5 structured sessions, interspersed with periods of self-directed learning. Cases are highly structured and contain all of the required information pertaining to the clinical problems presented. RESULTS: Evaluations of this course over 4 years by both students and teachers have been outstanding, with students consistently stating in their written comments that the PBL experience was one of the most meaningful learning experiences they have encountered during the pre-clinical phase of their training. CONCLUSIONS: This brief PBL experience appears to help in building up the students' clinical competence during their first clerkship experiences. It may be especially useful for medical schools using the traditional medical curriculum.

Early clinical heterogeneity in choreoacanthocytosis.

BACKGROUND: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. OBJECTIVE: To describe the early clinical features and possible genotype-phenotype correlation in CHAC. DESIGN AND SETTING: Case series in a tertiary care center. PATIENTS AND MAIN OUTCOME METHODS: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. RESULTS: Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. CONCLUSIONS: These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.

Frequent misdiagnosis of adult polyglucosan body disease.

Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to potentially harmful therapeutic interventions. To examine the frequency of misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30 patients diagnosed between 1991 and 2013. Diagnosis was based on the combination of typical clinical and imaging findings, reduced glycogen branching enzyme activity, and the presence of p.Y326S GBE1 mutation. Initial symptoms started in the 5th-6th decade with bladder dysfunction (47 %), gait problems (33 %) or both. Diagnosis of APBD was delayed by 6.8 (±4.8) years. Consistent signs at diagnosis were spasticity in the legs (93 %), decreased or absent ankle reflexes (100 %), bilateral extensor plantar response (100 %) and distal sensory deficit (80 %). Nerve conduction study showed invariable sensorimotor polyneuropathy, and MRI demonstrated cervical spinal cord atrophy (100 %) and leukoencephalopathy (97 %). All 30 patients were initially misdiagnosed. Common misdiagnoses included cerebral small vessel disease (27 %), multiple sclerosis (17 %), amyotrophic lateral sclerosis (17 %) and peripheral neuropathies (20 %). Consequently, 27 % received inappropriate therapy. In addition, lower urinary tract symptoms in 60 % of men were attributed solely to prostatic disorders but did not respond to medical treatment or prostatectomy. These findings suggest that despite limited clinical variability, APBD is invariably misdiagnosed and patients are often mistreated. Physicians' unfamiliarity with the typical clinical and imaging features of APBD appears as the main reason for misdiagnosis.

Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family.

BACKGROUND: Frontotemporal dementia with parkinsonism linked to chromosome 17q21-22 (FTDP-17) is an autosomal dominant tauopathy manifested by a variable combination of personality changes, cognitive decline and hypokinetic-rigid movement disorder. Significant clinical and pathological heterogeneity of FTDP-17 is related in part to more than 20 different pathogenic mutations identified in the tau gene. Among others, the P301S mutation has been previously reported in three families of European and one of Japanese origin presenting with different clinical phenotypes. OBJECTIVES: To report a three-generation family of Jewish-Algerian origin with FTDP-17 due to the P301S tau mutation. METHODS: Clinical, neuropsychological and neuroimaging evaluation of 3 patients, tau genotyping, and pathological study of the proband. RESULTS: The 3 affected family members had a fairly stereotyped clinical course with early personality changes from their late 30s followed within a period of 1-2 years by a progressive cognitive and motor deterioration eventually leading to a state of akinetic mutism or death 3-5 years after the initial symptoms. The main clinical manifestations included severe dementia and hypokinetic-rigid movement disorder associated with supranuclear gaze impairment, pyramidal signs and frontal release signs. Brain imaging disclosed a variable degree of frontotemporal atrophy, ventriculomegaly and regional cerebral hypoperfusion or glucose hypometabolism. Frontal lobe biopsy in the proband revealed weak tau immunoreactivity in a few cortical neurons, in rare neurites and in some glial cells with no neurofibrillary tangles. Molecular DNA analysis identified a P301S mutation in exon 10 of the tau gene. CONCLUSIONS: The observed clinical features further expand the reported P301S phenotype and confirm a more aggressive course of the disease than in the other known tau mutations.