Cutaneous malignant melanoma and Parkinson disease: Common pathways?

The mechanisms underlying the high prevalence of cutaneous malignant melanoma (CMM) in Parkinson disease (PD) are unclear, but plausibly involve common pathways. 129Ser‐phosphorylated α‐synuclein, a pathological PD hallmark, is abundantly expressed in CMM, but not in normal skin. In inherited PD, PARK genes harbor germline mutations; the same genes are somatically mutated in CMM, or their encoded proteins are involved in melanomagenesis. Conversely, genes associated with CMM affect PD risk. PD/CMM‐targeted cells share neural crest origin and melanogenesis capability. Pigmentation gene variants may underlie their susceptibility. We review putative genetic intersections that may be suggestive of shared pathways in neurodegeneration/melanomagenesis. Ann Neurol 2016;80:811–820     

Cytokines and depression: fortuitous or causative association?

There is an increasingly impressive database concerning the possible involvement of cytokines in depression and their role in the therapeutic effects of antidepressants. Based on the discussions which took place on these issues at a recent meeting held in Roscoff, France, this perspective summarizes in a critical way the evidence in favor of such a possibility, and points out the needs for further research to clarify both the nature of the subtle dysregulations that affect neuroendocrine-immune interactions in depressive disorders and their contribution to psychopathology.     

Malignant melanoma and levodopa in Parkinson's disease: causality or coincidence?

Levodopa is the major drug used in the treatment of patients with Parkinson's disease. However, levodopa continues to be ‘contra-indicated’ for patients with Parkinson's disease associated with malignant melanoma. Case reports have suggested that levodopa has a causal relationship with malignant melanoma due to their shared dopamine biochemical pathway. Clinical characteristics of 54 patients with both Parkinson's disease and melanoma were analyzed (43 cases from the literature and 11 from our institution). The results suggest that the occurrence of both Parkinson's disease and melanoma in these patients is coincidental rather than causal. It did not appear that the Parkinson's disease patients on levodopa therapy were predisposed to melanoma, nor did levodopa therapy appear to exaggerate melanoma if it were previously present.     

Amyotrophic lateral sclerosis and myasthenia gravis: association or chance occurrence?

Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/10⁹), compared to our findings (1.87/10⁷) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events.     

Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?

Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein‐related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. © 2016 International Parkinson and Movement Disorder Society     

Multiple sclerosis and non-communicating syringomyelia: a casual association or linked diseases?

Non-communicating syringomyelia (NCS) can be associated with different disease processes such as arachnoidytis, trauma or tumor. Approximately 12 cases, documented radiographically, of the association of non-communicating syringomyelia and multiple sclerosis (MS) have been described but their relationship remains obscure. In 3 patients with laboratory supported MS spinal magnetic resonance imaging (MRI) revealed a central cystic cavity. In 2 patients lesions on the spinal cord above the cavity were demonstrated. At 3-year follow-up in 1 patient, no change in the cavity was detected. Although 3 cases are insufficient for providing a definitive conclusion on the relationship between these two diseases, we suggest that demyelinating lesions have to be regarded as possible causes of spinal, asymptomatic cavities.     

Mitempfindung in synaesthetes: co-incidence or meaningful association?

Mitempfindung is the referral of a tactile sensation to a location far away from the stimulation site. This brief note reports a 40% incidence of Mitempfindung in a sample of 20 digit-color synaesthetes which contrasts with a 10% incidence in two control groups of non-synaesthetes. Phenomenological similarities between Mitempfindung and synaesthesia are discussed, and we propose that an erratic neural connectivity underlies both phenomena. To better characterize the nature of the purported neurophysiological peculiarities, prospective studies are needed that characterize Mitempfindung in synaesthetes and nonsynaesthetes.     

Mothers' mental illness and child behavior problems: cause-effect association or observation bias?

OBJECTIVE: A number of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior. METHOD: This prospective, longitudinal study examines data on the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems. RESULTS: Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths in reporting behavior problems appear to be related to the mothers' mental health. CONCLUSIONS: Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.     

Lumbar puncture and dural sinus thrombosis--a causal or casual association?

BACKGROUND: A few cases of cerebral venous thrombosis (CVT) were reported after a lumbar puncture (LP), suggesting a causal association. The purpose of our study was to document that LP might predispose to CVT by decreasing blood flow velocities (BFV) in veins or dural sinus. METHODS: We performed a transcranial Doppler ultrasound study to register the mean BFV of the straight sinus (SS) before, during and after LP. RESULTS: Thirteen patients were studied. LP induced a decrease of 47% of mean BFV in the SS. The mean decrease of BFV was significant immediately at the end (p = 0.003), 30 min after (p = 0.015) and more than 6 h after LP (p = 0.008). CONCLUSIONS: LP induced a sustained decrease of mean BFV in the SS. The decrease of venous blood flow is a possible mechanism contributing to the occurrence of CVT.