Fidias E. Leon-Sarmiento

Profound Olfactory Dysfunction in Myasthenia Gravis

In this study we demonstrate that myasthenia gravis, an autoimmune disease strongly identified with deficient acetylcholine receptor transmission at the post-synaptic neuromuscular junction, is accompanied by a profound loss of olfactory function. Twenty-seven MG patients, 27 matched healthy controls, and 11 patients with polymiositis, a disease with peripheral neuromuscular symptoms analogous to myasthenia gravis with no known central nervous system involvement, were tested. All were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT), a test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds. The UPSIT scores of the myasthenia gravis patients were markedly lower than those of the age- and sex-matched normal controls [respective means (SDs) = 20.15 (6.40) & 35.67 (4.95); p<0.0001], as well as those of the polymiositis patients who scored slightly below the normal range [33.30 (1.42); p<0.0001]. The latter finding, along with direct monitoring of the inhalation of the patients during testing, implies that the MG-related olfactory deficit is unlikely due to difficulties sniffing, per se. All PIT scores were within or near the normal range, although subtle deficits were apparent in both the MG and PM patients, conceivably reflecting influences of mild cognitive impairment. No relationships between performance on the UPSIT and thymectomy, time since diagnosis, type of treatment regimen, or the presence or absence of serum anti-nicotinic or muscarinic antibodies were apparent. Our findings suggest that MG influences olfactory function to the same degree as observed in a number of neurodegenerative diseases in which central nervous system cholinergic dysfunction has been documented.

Abnormality of motor cortex excitability in peripherally induced dystonia

It is widely accepted that peripheral trauma such as soft tissue injuries can trigger dystonia, although little is known about the underlying mechanism. Because peripheral injury only rarely appears to elicit dystonia, a predisposing vulnerability in cortical motor areas might play a role. Using single and paired‐pulse pulse transcranial magnetic stimulation, we evaluated motor cortex excitability of a hand muscle in a patient with peripherally induced foot dystonia, in her brother with craniocervical dystonia, and in her unaffected sister, and compared their results to those from a group of normal subjects. In the patient with peripherally induced dystonia, we found a paradoxical intracortical facilitation at short interstimulus intervals of 3 and 5 milliseconds, at which regular intracortical inhibition (ICI) occurred in healthy subjects. These findings suggest that the foot dystonia may have been precipitated as the result of a preexisting abnormality of motor cortex excitability. Furthermore, the abnormality of ICI in her brother and sister indicates that altered motor excitability may be a hereditary predisposition. The study demonstrates that the paired‐pulse technique is a useful tool to assess individual vulnerability, which can be particularly relevant when the causal association between trauma and dystonia is less evident.

Taste function in early stage treated and untreated Parkinson’s disease

Since brain stem regions associated with early Parkinson’s disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [99mTc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue.

Olfactory dysfunction in Parkinson's disease: Positive effect of cigarette smoking.

There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinsons disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal nonmotor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population.

Auditory and Lower Limb Tactile Prepulse Inhibition in Primary Restless Legs Syndrome: Clues to Its Pathophysiology.

Summary: The resting sensory discomfort transiently relieved upon movement of the affected area in restless legs syndrome suggests that sensorimotor integration mechanisms, specifically gating, may be altered in the disease. The authors sought to determine the effects of prepulse auditory and tactile stimulation applied to lower limbs on the blink reflex of patients with restless legs syndrome and healthy subjects. Seventeen patients with restless legs syndrome and 17 age- and sex-matched healthy controls were investigated. Auditory stimuli and tactile lower limb stimulation were applied as prepulses. The R2 response of the blink reflex induced by electrical stimulation applied to the right supraorbital nerve was selected as the test stimulus. Time intervals between prepulses and response-eliciting stimuli were 40, 70, 90, 110, and 200 milliseconds. There were no differences in either the auditory or tactile prepulse conditions between patients and controls and no differences between these measures within subject groups. We concluded that the tactile lower limb and the auditory prepulse effects on the brainstem interneurons mediating the blink reflex share common neural pathways. Because forebrain interneurons mediate these prepulse effects, they are likely not involved in the disordered sensorimotor interaction of restless legs syndrome.

Novel Mechanisms Underlying Inhibitory and Facilitatory Transcranial Magnetic Stimulation Abnormalities in Parkinson's Disease

BACKGROUND AND AIMS The motor-evoked potential (MEP) induced by transcranial magnetic stimulation (TMS), its recruitment and the conditioning effects of weak stimuli in Parkinsons disease (PD) have shown contradictory results. The aim of this study is to definitively establish the influences of PD on the TMS-evoked MEP. METHODS We investigated resting and active motor thresholds, resting and active recruitment curves, and short interval intracortical inhibition (ICI) and facilitation (ICF) in 39 PD patients and 40 age-matched healthy controls. The Unified Parkinsons Disease Rating Scale (UPDRS) motor score was used as a clinical measure. RESULTS MEPs to single pulses were slightly, but significantly, larger in the PD patients at rest, but increased much less than controls with voluntary muscle activation. PD patients also showed clearly and consistently less ICI and ICF by the conditioning pulse. Both ICI and ICF correlated with MEP threshold in healthy subjects, but not in PD patients. None of the TMS measures correlated with the UPDRS. CONCLUSIONS This study strongly supports the view that PD-related MEPs reflect a disturbed signal-noise ratio of pyramidal neuron responses. Such disturbance may be due to a complex combination of altered presynaptic and surround inhibition that results in unbalanced excitatory/inhibitory input at the brain motor cortex level.

The lateralized smell test for detecting Alzheimer's disease: Failure to replicate

OBJECTIVES A widely publicized study by Stamps, Bartoshuk and Heilman (2013) reported that a simple measure of left:right naris differences in the ability to detect the odor of peanut butter is a sensitive marker of Alzheimers disease (AD). AD patients were said to have abnormal smell function on the left side of the nose and normal function on right side of the nose. In light of its implications for medical practice and the world-wide publicity that it engendered, we sought to replicate and expand this work. METHODS Two studies were performed. In the first, 15 AD patients were tested according to the procedures described by Stamps et al. in which the nostril contralateral to the tested side was occluded by the patient using lateral pressure from the index finger. Since this can potentially distort the contralateral naris, we repeated the testing using tape for naris occlusion. In the second, 20 AD patients were administered 20 odors of the University of Pennsylvania Smell Identification Test (UPSIT) to each side of the nose, with the contralateral naris being closed with tape. In both studies, the order of the side of testing was systematically counterbalanced. RESULTS No evidence of a left:right asymmetry on any test measure was observed. CONCLUSION Although hyposmia is well-established in AD, no meaningful asymmetry in smell perception is apparent. If olfactory function on the right side of the nose was normal as claimed, then AD patients should exhibit normal function when tested bilaterally, a phenomenon not seen in dozens of AD-related olfactory studies.

Primary and Reversible Pisa Syndrome in Juvenile Normal Pressure Hydrocephalus.

Objective To report a case of Pisa syndrome in a patient with idiopathic normal pressure hydrocephalus, who had never been exposed to psychotropic medications. Methods A 26-year-old, Colombian, male patient, was referred because he had cognitive abnormalities, gait disturbances and urinary incontinence. This patient also displayed pleurothotonos. Neurofunctional evaluations of sensory and motor integration at peripheral and central nervous system levels were done. Idiopathic normal pressure hydrocephalus (NPH) was diagnosed. Results Pisa syndrome disappeared after spinal tap drainage with further gait, balance and behavioural improvement. A brainstem-thalamocortical deregulation of the central sensory and motor programming, due to the chaotic enlargement of brain ventricles was thought to be the pathophysiological mechanism underlying this case. Conclusion NPH must not be longer considered as an exclusive geriatric disorder. Further, uncommon movement disorders may appear with this disorder, which should be carefully approached to avoid iatrogenic and deleterious pharmacological interventions.

Suprathreshold odor intensity perception in early‐stage Parkinson's disease

Whether Parkinsons disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimers disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age‐ and disease‐related pathological conditions.

Pathophysiology of movement disorders due to gravity transitions: The channelopathy linkage in human balance and locomotion

Despite theoretical and experimental efforts to understand the space adaptation syndrome (SAS), which is responsible for spatial disorientation that severely affects physical and cognitive performance in astronauts, most of its pathophysiology is still unknown. As a consequence, countermeasures for SAS are not completely effective. Accordingly, in addition to the sensory-motor conflict theories, we propose that microgravity would affect the potassium channels of inner ear hair cells that would result in a temporal channelopathy as the most likely molecular origin for SAS, as well as being responsible for perpetuating movement disorders in gravity transition environments including those to be experienced by people visiting or living on the earth, moon, mars and beyond.