Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae?

An abnormally frequent atypical levodopa-unresponsive, akinetic-rigid syndrome with some similarity to PSP was identified in the Caribbean island Guadeloupe, and was associated with the consumption of plants of the Annonacea family, especially Annona muricata (corossol, soursop) suggesting a possible toxic etiology. Annonaceae contain two groups of potential toxins, alkaloids and acetogenins. Both alkaloids and annonacin, the most abundant acetogenin, were toxic in vitro to dopaminergic and other neurons. However we have focused our work on annonacin for two reasons: (1) annonacin was toxic in nanomolar concentrations, whereas micromolar concentrations of the alkaloids were needed, (2) acetogenins are potent mitochondrial poisons, like other parkinsonism-inducing compounds. We have also shown that high concentrations of annonacin are present in the fruit or aqueous extracts of the leaves of A. muricata, can cross the blood brain barrier since it was detected in brain parenchyma of rats treated chronically with the molecule, and induced neurodegeneration of basal ganglia in these animals, similar to that observed in atypical parkinsonism. These studies reinforce the concept that consumption of Annonaceae may contribute to the pathogenesis of atypical parkinsonism in Guadeloupe.     

Is schizoaffective disorder a useful diagnosis?

A diagnosis of schizoaffective disorder is frequently used to describe a psychotic person with significant symptoms of depression and/or mania. The word schizoaffective was introduced by Jacob Kasanin in 1933 and has appeared in all editions of the DSM since 1952. However, the current DSM-IV-TR diagnosis of schizoaffective disorder is not reliable and is of limited clinical utility. The validity is built primarily on the prediction of course and outcome and on emerging findings from genetic and neurobiological studies. This review of the current status of schizoaffective disorder concludes with several suggestions for a revision of the diagnosis within a categorical or dimensional nosology of psychotic and affective disorders.     

Is retinal photography useful in the measurement of stroke risk?

BACKGROUND: The retinal microcirculation can be viewed non-invasively to give a unique perspective of the cerebral microcirculation in vivo. Studying pathological changes of retinal blood vessels (microaneurysms, retinal haemorrhages, and retinal arteriolar narrowing) may help to understand the causes of various cerebrovascular disorders. Retinal photography provides such an opportunity. RECENT DEVELOPMENTS: Several recent studies have shown that retinal microvascular changes are reliably documented by retinal photographs. These retinopathy changes seem to be fairly common in the general population, even in people without hypertension or diabetes. Retinopathy is related to incident clinical stroke and stroke mortality and to MRI-defined subclinical cerebral white-matter lesions and cerebral atrophy, independent of blood pressure, diabetes, and other cerebrovascular risk factors. WHERE NEXT?: Retinal microvascular abnormalities seem to be markers of concomitant cerebral microangiopathy, and retinal photography may be useful for the investigation of microvascular disorders of the brain in clinical and epidemiological settings. Future research should be aimed at the development of standardised photographic methods for the assessment of retinal microvascular changes, the replication of these findings in other populations and in people with other cerebrovascular disorders, and the examination of the increased accuracy of stoke-risk stratification given by retinal photography     

Dementia with parkinsonism: what is the diagnosis?

The case presented highlights the difficult differential diagnosis of dementia with parkinsonism. Many disorders affecting the frontal-subcortical circuits produce the triad of impaired cognition, movement disorder, and neuropsychiatric symptoms. The 72-year-old patient whose case is reviewed here had abnormalities in all three domains.     

Is EEG useful in assessing patients with acute encephalitis treated with acyclovir?

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P<0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau −0.6, P=0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P=0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.     

Is the VBR still a useful measure of changes in the cerebral ventricles?

Standard methods of ventricular measurement with computed tomography (CT) and magnetic resonance imaging (MRI) allow for as much as a 10-mm variation in the level of the "best" axial slice through the lateral ventricles. In a series of 10 patients who received MRI scans, the effect of 1-mm variations in slice center level on measured ventricle-brain ratio (VBR) was determined; even variations as small as 1 mm can result in a 10% change in VBR. The amount of within-subject variability in VBR that could result from this factor alone appears to be more than twice as large as that encountered with direct volume measurements, indicating that the latter measure would be at least twice as sensitive to real changes in ventricular size as the VBR.     

How useful are anti-neural IgM antibodies in the diagnosis of chronic immune-mediated neuropathies?

Antibodies against several neural antigens have been associated with different chronic immune-mediated neuropathies but their practical clinical relevance remains unclear. To determine the possible diagnostic usefulness of these antibodies we reviewed the clinical correlate of IgM antibodies to the myelin-associated glycoprotein (MAG), sulfatide, the gangliosides GM1, GM2, GD1a and GD1b in 539 consecutive patients examined for neuropathy or related diseases in our Neuropathy Clinics and tested for these antibodies in our laboratory since 1985. 302 patients (56%) had an established diagnosis of definite or possible chronic immune-mediated neuropathy while 237 had a neuropathy of non-immune-mediated origin or of unknown aetiology or a closely related disease. Antibodies to one or more antigen were more frequent (chi(2)=63.32; p<0.00001) in patients with chronic immune-mediated neuropathy (37.7%) than with other neuropathy or related diseases (7.2%) and their presence was associated in 87% of the patients with an immune-mediated neuropathy, incrementing by 31% the probability of having this form. Testing for MAG permitted to identify 24.8% of patients with an immune-mediated neuropathy, GM1 an additional 9.9%, while GM2, GD1b, GD1a and sulfatide altogether an additional 3% of the patients. Concerning clinical correlations, all 75 patients with anti-MAG IgM had neuropathy and IgM monoclonal gammopathy (PN+IgM) with a positive predictive value for this neuropathy of 100%. A similarly high predictive value for neuropathy (91.4%) was observed among 269 patients with IgM monoclonal gammopathy including 103 patients without neuropathy. Anti-sulfatide IgM, though rare, were also significantly and constantly associated with PN+IgM and permitted to identify few patients not bearing anti-MAG IgM. Anti-GM1 IgM were significantly associated with multifocal motor neuropathy (MMN) (29.2%) but where also found in a few patients with other immune or non-immune neuropathies or related diseases with a positive predictive value for MMN of 25.5%. Anti-GM2 IgM were also significantly associated with MMN and increased the sensitivity (36.2%) for MMN obtained with anti-GM1 IgM only, without affecting its specificity and positive predictive value. Anti-GD1a, GD1b, though not significantly more frequent in patients with immune-mediated neuropathy, were associated in 80 to 100% of patients with these neuropathies. In conclusion anti-neural IgM antibodies may help in identifying patients with a chronic immune-mediated neuropathy, even if only anti-MAG and anti-sulfatide IgM appear to be strictly associated with a definite clinical syndrome.     

What’s shaking in the ICU? The differential diagnosis of seizures in the intensive care setting

To analyze what conditions mimic seizures in the intensive care unit (ICU) setting, we reviewed all bedside electroencephalography (EEG)–videos obtained in the adult ICU setting over an 18‐month period. Only those studies performed for “possible seizures” due to motor phenomena and whose clinical events were captured on video were analyzed. A total of 52 studies were performed. Fourteen patients (27%) had epileptic seizures. Thirty‐eight (73%) had nonepileptic events. These consisted of 12 (23%) with tremor‐like movements, 7 (13.5%) with multifocal myoclonic jerks without electrographic changes, 7 (13.5%) with slow semipurposeful movements, and 10 with other movements. Therefore, seizure mimics in the ICU setting were diverse and distinct from the usual differential diagnosis of seizures seen in ambulatory patients.     

Is cerebral white matter involvement helpful in the diagnosis of dentatorubral-pallidoluysian atrophy?

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cerebellar ataxia in combination with variable neurological symptoms. Cerebral white matter involvement of DRPLA is rare and reported mainly in severe, progressed cases of old-aged or juvenile-onset DRPLA. We describe three cases of genetically confirmed DRPLA that developed changes in cerebral white matter in the early stage of middle-aged patients. Our results of our study indicate that cerebral white matter changes are not rare in DRPLA and might be helpful for differentiation in ataxia patients with brainstem and cerebellum atrophy.     

Is methamphetamine abuse a risk factor in parkinsonism?

Parkinsons disease (PD) is a neurodegenerative disorder with increased incidence in individuals beyond 50 years of age. The etiology of PD is currently not known, but it appears that environmental factors may play an important role. The molecular basis of PD is the nearly complete loss of the neurotransmitter dopamine (DA) in the basal ganglia (caudate/putamen). The decrease in dopamine levels is the result of degeneration of dopamine-containing neurons in the substantia nigra. This biochemical deficit in the nigrostriatal pathway leads to the emergence of motor impairments typical of PD. Methamphetamine (METH) is a psychostimulant drug with increasing use in certain segments of the population in the United States and worldwide. In experimental animal models and human studies, METH administration has been shown to decrease markers of dopaminergic neuron terminal integrity in the basal ganglia. A long-standing question has been whether the reductions in dopaminergic markers induced by METH constitute degenerative changes or reflect drug-induced modulation. Resolving this question is important because the irreversible loss of dopaminergic function may increase the likelihood of Parkinsonism with advancing age.