Faculty Bibliography

Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 mug daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible

Paraneoplastic neurological syndromes (PNS) are rare manifestations of malignant disease. It is currently believed that most, if not all, PNS are autoimmune in nature. Proteins expressed on the surface of tumor cells trigger an immune response that cross-reacts with similar proteins in the nervous system, resulting in damage. Moreover, recent studies propose that the appearance of autoimmune phenomena in patients with malignant melanoma implies a strong antitumoral activity and constitutes a marker of improvement in overall survival. We describe a most unusual case of chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in a patient with metastatic malignant melanoma of unknown primary origin who received treatment with interferon alpha-2b. We also review the relevant literature about this infrequent association, discuss on its pathogenesis and underline its importance as surrogate marker, useful to verify the antineoplastic treatment efficacy.

Background: Panic disorder (PD) patients have been shown to have reduced heart rate variability (HRV). Low HRV has been associated with elevated risk for cardiovascular disease. Our aim was to investigate the effects of treatment on heart rate (HR) in patients with PD through a hyperventilation challenge. Methods: We studied 54 participants, 43 with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) PD and 11 controls. Subjects lay supine with their heads in a plastic canopy chamber, resting for 15 min and then breathing at a rate of 30 breaths per minute for 10 min. HRV was sampled for spectral analysis. Clinical and behavioral measures of anxiety were assessed. Treatment was chosen by patients: either 12 weeks of CBT alone or CBT with sertraline. Results: All patients showed significant decrease on clinical measures from baseline and 31 were treatment responders, 8 dropped out of the study before completion of the 12-week treatment phase and 4 were deemed nonresponders after 12 weeks of treatment. Although both treatments led to significant clinical improvement, only CBT alone demonstrated a significant reduction in HR and increase in HRV. Conclusions: Our study replicated the finding that increased HR and decreased HRV occur in PD patients. Given the evidence of cardiac risk related to HRV, CBT appears to have additional benefits beyond symptom reduction. The mechanisms of this difference between CBT and sertraline are unclear and require further study. Depression and Anxiety 0:1-8, 2008. (c) 2008 Wiley-Liss, Inc

To clarify whether the R3 component of the electrically elicited blink reflex is a nociceptive response we studied two patients with congenital insensitivity to pain due to the impaired development of Adelta and C nerve fibers (hereditary sensory and autonomic neuropathy types III and IV). We postulated that if the R3 component is a nociceptive reflex, it should be absent in these patients. The R3 responses were elicited in both sides in both the patients at all intensities, strongly suggesting that the R3 component of the blink reflex is not a nociceptive response

OBJECTIVE: To determine whether the heart rate changes during tilt table testing could be used in the differential diagnosis between vasovagal syncope and chronic autonomic failure. METHODS: We compared the relationship between electrocardiographic R-R intervals and beat-to-beat blood pressure in 43 patients with typical vasovagal responses and 30 patients with chronic autonomic failure (6 pure autonomic failure, 23 multiple system atrophy, and 1 Parkinson's disease). RESULTS: In every patient with vasovagal syncope, at the time when the blood pressure was falling, it was possible to identify at least 12 successive heart beats (mean 33 +/- 2 heart beat, range 12-57) when blood pressure and heart rate fell in parallel, i.e., there was a negative relationship between blood pressure and R-R intervals (P < 0.001). In contrast, the relationship between blood pressure and R-R intervals in patients with chronic autonomic failure was never negative, i.e., heart rate always increased, albeit less than expected for the given fall in blood pressure, or remained unchanged. INTERPRETATION: The heart rate changes during the fall in blood pressure can distinguish patients with vasovagal responses from those with chronic autonomic failure

BACKGROUND: A consensus conference on multiple system atrophy (MSA) in 1998 established criteria for diagnosis that have been accepted widely. Since then, clinical, laboratory, neuropathologic, and imaging studies have advanced the field, requiring a fresh evaluation of diagnostic criteria. We held a second consensus conference in 2007 and present the results here. METHODS: Experts in the clinical, neuropathologic, and imaging aspects of MSA were invited to participate in a 2-day consensus conference. Participants were divided into five groups, consisting of specialists in the parkinsonian, cerebellar, autonomic, neuropathologic, and imaging aspects of the disorder. Each group independently wrote diagnostic criteria for its area of expertise in advance of the meeting. These criteria were discussed and reconciled during the meeting using consensus methodology. RESULTS: The new criteria retain the diagnostic categories of MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia to designate the predominant motor features and also retain the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease including parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality. CONCLUSIONS: These new criteria have simplified the previous criteria, have incorporated current knowledge, and are expected to enhance future assessments of the disease.

Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders

OBJECTIVE: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain. METHODS: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and the selected indications. Authors reviewed, abstracted, and classified articles based on the quality of the study (Class I-IV). Conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. RESULTS: The highest quality literature available for the respective indications was as follows: axillary hyperhidrosis (two Class I studies); palmar hyperhidrosis (two Class II studies); drooling (four Class II studies); gustatory sweating (five Class III studies); neurogenic detrusor overactivity (two Class I studies); sphincter detrusor dyssynergia in spinal cord injury (two Class II studies); chronic low back pain (one Class II study); episodic migraine (two Class I and two Class II studies); chronic daily headache (four Class II studies); and chronic tension-type headache (two Class I studies). RECOMMENDATIONS: Botulinum neurotoxin (BoNT) should be offered as a treatment option for the treatment of axillary hyperhidrosis and detrusor overactivity (Level A), should be considered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B), and may be considered for gustatory sweating and low back pain (Level C). BoNT is probably ineffective in episodic migraine and chronic tension-type headache (Level B). There is presently no consistent or strong evidence to permit drawing conclusions on the efficacy of BoNT in chronic daily headache (mainly transformed migraine) (Level U). While clinicians' practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data