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 Alzheimer's 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.

[Present and future of the transcranial magnetic stimulation]. / Presente y futuro de la estimulación magnética transcraneal.

Magnetic stimulation has called the attention of neuroscientists and the public due to the possibility to stimulate and "control" the nervous system in a non-invasive way. It has helped to make more accurate diagnosis, and apply more effective treatments and rehabilitation protocols in several diseases that affect the nervous system. Likewise, this novel tool has increased our knowledge about complex neural behavior, its connections as well as its plastic modulation. Magnetic stimulation applied in simple or paired-pulse protocols is a useful alternative in the diagnosis of diseases such as multiple sclerosis, Parkinson disease, epilepsy, dystonia, amyotrophic lateral sclerosis, cerebrovascular disease, and sleep disorders. From the therapeutic perspective, magnetic stimulation applied repetitively has been found useful, with different degrees of efficacy, in treating resistant depression, tinnitus, psychogenic dysphonia, Alzheimer disease, autism, Parkinson disease, dystonia, stroke, epilepsy, generalized anxiety as well as post traumatic stress disorder, auditory hallucinations, chronic pain, aphasias, obsessive-compulsive disorders, L-dopa induced dyskynesia, mania and Rasmussen syndrome, among others. The potential of magnetic stimulation in neurorehabilitation is outstanding, with excellent range of safety and, in practical terms, without side effects.

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 Parkinson's 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 Parkinson's 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.

Presente y futuro de la estimulación magnética transcraneal / Present and future of the transcranial magnetic stimulation

La estimulación magnética transcraneal ha llamado la atención de neurocientíficos y público en general por la posibilidad de estimular y “controlar” el sistema nervioso de forma no invasiva, realizar diagnósticos más exactos, y aplicar tratamientos y programas de rehabilitación más efectivos en múltiples enfermedades que afectan el sistema nervioso. Así mismo, esta novedosa herramienta ha ayudado a develar la complejidad del comportamiento neural, sus conexiones y su modulación plástica. La estimulación magnética aplicada de manera simple o pareada, se ha convertido en una alternativa útil en el diagnóstico de enfermedades como esclerosis múltiple, enfermedad de Parkinson, epilepsia, distonía, esclerosis lateral amiotrófica, enfermedad cerebro vascular, así como el sueño y sus trastornos, entre otras alteraciones. A nivel terapéutico, se ha sugerido el uso de la estimulación magnética repetitiva con diferentes niveles de evidencia en depresión refractaria a tratamiento farmacológico convencional, tinitus, afonía psicógena, enfermedad de Alzheimer, autismo, enfermedad de Parkinson, distonías, accidente cerebro vascular, epilepsia, trastornos de ansiedad generalizada, estrés post-traumático, alucinaciones auditivas, dolor crónico, afasias, trastorno obsesivo compulsivo, disquinesias inducidas por L-Dopa, manía y síndrome de Rasmussen, entre otros trastornos. Su beneficio en neurorehabilitación es una realidad inocultable, en cuyo caso se ha podido usar con efectividad y, prácticamente, sin efectos secundarios.

Magnetic stimulation has called the attention of neuroscientists and the public due to the possibility to stimulate and “control” the nervous system in a non-invasive way. It has helped to make more accurate diagnosis, and apply more effective treatments and rehabilitation protocols in several diseases that affect the nervous system. Likewise, this novel tool has increased our knowledge about complex neural behavior, its connections as well as its plastic modulation. Magnetic stimulation applied in simple or paired-pulse protocols is a useful alternative in the diagnosis of diseases such as multiple sclerosis, Parkinson disease, epilepsy, dystonia, amyotrophic lateral sclerosis, cerebrovascular disease, and sleep disorders. From the therapeutic perspective, magnetic stimulation applied repetitively has been found useful, with different degrees of efficacy, in treating resistant depression, tinnitus, psychogenic dysphonia, Alzheimer disease, autism, Parkinson disease, dystonia, stroke, epilepsy, generalized anxiety as well as post traumatic stress disorder, auditory hallucinations, chronic pain, aphasias, obsessive-compulsive disorders, L-dopa induced dyskynesia, mania and Rasmussen syndrome, among others. The potential of magnetic stimulation in neurorehabilitation is outstanding, with excellent range of safety and, in practical terms, without side effects.

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.

WITHDRAWN: Mechanisms Underlying Inhibitory and Facilitatory Transcranial Magnetic Stimulation Abnormalities in a Large Sample of Patients with Parkinson's Disease.

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Neuroplasticidad, Neuromodulación y Neurorrehabilitación: Tres conceptos distintos y un solo fin verdadero / Neuroplasticity, Neuromodulation and Neurorehabilitation: Three different concepts, one only true goal

El sistema nervioso es un sistema cerrado pero, a la vez, muy dinâmico, que asimila, reorganiza y modifica los mecanismos biológicos, bioquímicos y fisiológicos que posee. Esta capacidad se denomina neuroplasticidad e implica cambios en el tejido neural que incluye regeneración axonal, colateralización, neurogenesis, sinaptogénesis y reorganización funcional, entre otros mecanismos. Dichos mecanismos emplean neurotrasmisores como el N-metil-D-apartato (NMDA), el ácido gama-aminobutirico (GABA), la acetilcolina o la serotonina, involucrados en la potenciación o depresión sinâptica a corto o largo plazo, la cual puede durar horas o días, sostenida por segundos mensajeros como el AMP cíclico, cuyos efectos pueden ser transitorios o permanentes. Estos efectos son la base de la neuromodulación. Esta última genera cambios a largo plazo en la actividad metabólica neuronal y su respuesta a diversos estímulos eléctricos, magnéticos o químicos, empleados en la neurorrehabilitación clínica. Dicha neurorrehabilitación es una intervención necesaria en, al menos, el 75% de los pacientes que han padecido un insulto neural, cuyo fundamento es la recuperación funcional del paciente. Por esto, la responsabilidad de los neurólogos clínicos, los neurocirujanos, los pediatras, los neuropediatras, los ortopedistas, los siquiatras y los cirujanos en general, entre otros profesionales de la salud, debería no solo proveer un diagnóstico y suministrar un tratamiento médico o quirúrgico, sino reorientar al paciente hacia un programa formal de neurorrehabilitación, liderado por especialistas en el área, en el que le ayudaran a alcanzar una apropiada funcionabilidad,una óptima neurorrestauración y una adecuada calidad de vida, incluyendo la de sus correspondientes familias.

The nervous system is a closed system but, at the same time, is very dynamic and able to adapt, reorganize and modify the biological, biochemical and physiological mechanisms that it poses. This ability is called neuroplasticity and implies changes in neural structures such as axonal regeneration, collateralization, neurogenesis, synaptogenesis and functional reorganization, among other mechanisms. These mechanisms involve different neurotransmitters such as N-metil-D-apartate (NMDA), gama-amynobutiric acid (GABA), acetilcholine or serotonine; they are involved in short-term depression and potentiation which may last hours or days, maintained by second messengers such as cyclic AMP; its effects may be transient or permanents, and they are the basis of neuromodulation. This latter concept involves long term changes on the neuronal metabolism and its responses to electrical, magnetic or chemical stimuli are employed for neurorehabilitation. Neurorehabilitation is an intervention that must be applied in, at least, seventy five percent of patients suffering neural injuries being its main goal the functional recovery of patients. Accordingly, clinical neurologist, neurosurgeons, pediatricians, neuropediatricians, orthopedic surgeons, psychiatrists and general surgeons, among other health care professionals should offer not only a diagnosis and its corresponding medical or surgical treatment, but also to reorient patients toward neurorehabilitation programs led by a specialist properly trained in this area. This will help patients to obtain optimal functioning, better neurorestaurative condition and a more appropriate quality of life of patients and their relatives.

[Magnetoreception: the angular stone in aerospace orientation, human balance and locomotion]. / Magnetorrecepción: la piedra angular de la orientación aeroespacial, balance y locomoción humana.

Current research is in agreement with the presence of a magnetic compass in living beings including humans. The two most accepted explanations that demonstrate the existence of magnetoreceptors in living beings are, the radical pair and the biogenic magnetite, which are discussed here with its respective experimental evidence and support. It indicates the presence of magnetite crystals in otoliths, among different inferior species of animals. Moreover, the magnetite found in several organs of human body allows predicting the existence of such element, in otoliths of vestibular system as well; further, anticipates that human magnetoreception is an additional function of the vestibular system. These geomagnetic signals would modulate balance, movement and spatial positioning of man in concordance of gravity values. This new field of otomagnetism opens new research areas for understanding the mechanisms involved in balance, equilibrium, orientation, and space positioning in normal and disease populations. Likewise, this could be the starting point for application of new human neurorehabilitation procedures, in those magnetoreception-associated neurological disorders that happen in the earth, the sea or the air.