Could a neurological disease be a part of Mozart's pathography?

As expected, since we recently celebrated the 250th anniversary of birth of Wolfgang Amadeus Mozart, there has been again a renewal of interest in his short but intensive life, as well as in the true reason of his untimely dead. Mozart lived and died in time when the medical knowledge was based mostly on subjective observations, without the established basics of standardized medical terminology and methodology. This leaves a great space for hypothesizing about his health problems, as well as about the cause of his death. The medical academic community attributed to Mozart approximately 150 different medical diagnoses. There is much speculation on the possible causes of Mozart's death: uremia, infection, rheumatic fever, trichinellosis, etc. Recently some authors have raised the question about a possible concomitant neurological disease. According to available records, Mozart has shown some elements of cyclotimic disorder, epilepsy and Gilles de la Tourette syndrome. Furthermore, the finding of a temporal fracture on (allegedly) Mozart's skull, gives a way to speculations about the possibility of a chronic subdural hematoma and its compressive effect on the temporal lobe. Despite numerous theories on Mozart's pathography that also include a concomitant neurological disorder, the medical and history records about Mozart's health status indicate that he probably had suffered from an infective illness, followed most likely by the reactivation of rheumatic fever, which was followed by strong immunologic reaction in the last days of his life. Taking all the above into consideration, it is reasonably to conclude that Mozart's neurological disturbances were caused by the intensity of the infective disease, and not primarily by a neurological disease.

Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report.

Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.

Self-Perceived Mental Health Status, Digital Activity, and Physical Distancing in the Context of Lockdown Versus Not-in-Lockdown Measures in Italy and Croatia: Cross-Sectional Study in the Early Ascending Phase of the COVID-19 Pandemic in March 2020.

The novelty of the coronavirus disease 2019 (COVID-19) pandemic is that it is occurring in a globalized society enhanced by digital capabilities. Our aim was to analyze the psychological and emotional states of participants in different pandemic-related contexts, with a focus on their digital and physical distancing behaviors. The online survey was applied during the ascending phase of the pandemic in March 2020 in two neighboring EU countries: Italy and Croatia. The study subjects involved four groups, two directly affected by epidemiological measures and two serving as controls-(1) participants from Italy who were in lockdown (Italy group), (2) participants from Croatia who were not in lockdown but who were in direct contact with an infected person and underwent epidemiological measures (CRO-contact group), (3) participants from Croatia who were in an analogous situation but not near the same infected person (CRO-no contact group), and (4) participants from Croatia who were not aware of any infected person (CRO-unrelated group). The survey consisted of validated scales of psychological and emotional states, and custom-made questionnaires on the digital (online) and physical (off-line) behavior of the participants. The Italy group in lockdown had higher self-perceived scores for depression, stress, post-traumatic intrusion, and avoidance, as well as the highest digital activity and physical distancing than the not-in-lockdown Croatian groups. The insight into the extent of online activities and off-line isolation allowed for the introduction of Digital Activity and Physical Distancing Scores. Self-perceived post-traumatic avoidance was higher in both the Italy and CRO-contact groups than the control CRO-no contact and CRO-unrelated groups, and higher avoidance correlated with higher Digital Activity and Physical Distancing Scores. Being in direct contact with the infected person, the CRO-contact group had no other alterations than unexpectedly lower post-traumatic hyperarousal when compared with the Italy group. The Italy group in lockdown demonstrated higher self-perceived psychological toll together with higher digital activity and physical distancing than Croatian groups not in lockdown, even when compared with the affected CRO-contact group. The study outcomes suggest that the general emergency measures influenced citizens in lockdown more than exposure to the virus through direct contact with an infected person.

Neuroanatomical basis of Sandifer's syndrome: a new vagal reflex?

Sandifer's syndrome is a gastrointestinal disorder with neurological features. It is characterized by reflex torticollis following deglutition in patients with gastroesophageal reflux and/or hiatal hernia. The authors believe that neurological manifestations of the syndrome are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii (NTS). Three models for the neuroanatomical basis of the hypothetic reflex arc are presented. In the first one the hypothetic reflex arc is based on the classic hypothesis of two components nervus accessorius (n.XI) - radix cranialis (RC) and radix spinalis (RS) The nervous impulses are transmitted by nervus vagus (n.X) general visceral afferent (GVA) fibers to NTS situated in medulla oblongata, then by interneuronal connections on nucleus ambiguus (NA) and nucleus dorsalis nervi vagi (NDX). Special visceral efferent fibers (SVE) impulses from NA are in part transferred to n.XI ramus externus (RE) (carrying the majority of general somatic efferent (GSE) fibers) via hypothetic anastomoses in the region of foramen jugulare. This leads to contraction of trapezius and sternocleidomastoideus muscles, and the occurrence of intermittent torticollis. In the second suggested neuroanatomical model the hypothetic reflex arc is organized in the absence of n.XI RC, the efferent part of the reflex arc continues as NA, which is motor nucleus of nervus glossopharyngeus (n.IX) and n.X in this case while distal roots of n.XI that appear at the level of the olivary nucleus lower edge represent n.X roots. In the third presented model the hypothetic reflex arc includes no jugular transfer and could be realized via interneuronal connections directly from NTS to the spinal motoneurons within nucleus radicis spinalis nervi accessorii (NRS n.XI) or from NA to NRS n.XI. The afferent segment of the postulated reflex arc in all three models is mediated via n.X. We conclude that Sandifer's syndrome is a clinical manifestation of another vagal reflex that could be termed a "vagocervical" or "esophagocervical" reflex, based on the neuroanatomical hypotheses elaborated in this paper.

Increased permeability of the blood-brain barrier following administration of glyceryl trinitrate in common carp (Cyprinus carpio L.).

Nitric oxide (NO) has been implicated in the pathogenesis of migraine and treatment with its exogenous donor glyceryl trinitrate (GTN) represents widely accepted experimental "migraine model". In this study, glyceryl trinitrate was administered intraperitoneally to carps, serum nitrite and nitrate levels were determined, permeability of blood-brain barrier was investigated, and histological changes of brain tissue were analyzed. Serum nitrite and nitrate levels displayed characteristic biphasic pattern with moderate initial increase and maximal terminal increase, suggesting the GTN-induced endogenous NO synthesis. Increased permeability of the blood-brain barrier in GTN-treated animals was determined based on Evans blue capillary leakage into the brain tissue. Histological analysis revealed changes consistent with vasodilatation and oedema. Our study strongly supports the importance of the NO role in the pathogenesis of migraine attacks and increase in blood-brain barrier permeability during the attack. The study has also provided evidence that this mechanism of action is conserved to the lower vertebrate.

Effects of nitric oxide on blood-brain barrier permeability in common carp (Cyprinus carpio L.).

OBJECTIVE: To determine in vivo effects of nitric oxide (NO) on blood-brain barrier (BBB) permeability in common carp (Cyprinus carpio L.). ANIMALS: 148 carp. PROCEDURES Carp received glyceryl trinitrate (1 mg/kg) as an NO donor or received no treatment (control group). Nitrite and nitrate concentrations in carp sera were determined 0.25, 1, 3, 6, 8, 12, and 24 hours after treatment. In control and treatment groups, BBB permeability was analyzed by assessment of leakage of Evans blue dye into various brain areas at 6, 12, and 24 hours after glyceryl trinitrate treatment. Brain edema was determined by means of the wet-dry weight method and assessed with light microscopy on H&E-stained preparations of tissues obtained 6 and 24 hours after glyceryl trinitrate treatment. RESULTS: Treatment with glyceryl trinitrate induced endogenous synthesis of NO, which was upregulated 6 and 8 hours after treatment. Increased NO synthesis was associated with increased permeability of the BBB, which developed 6 hours after treatment with the NO donor. Although the BBB became impermeable again by 12 hours after glycerol trinitrate treatment, brain edema still persisted 24 hours after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, treatment with an NO donor caused reversible opening of the BBB and brain edema in common carp. An intact BBB is important to prevent influx of potentially harmful substances into the brain. This investigation highlighted the possibility of BBB disarrangement caused by NO, a substance found in the CNS of all vertebrates evaluated.

Visual evoked potentials in patients with pineal gland cyst.

AIMS: The functional effect of the pineal gland cyst is difficult to evaluate with visual field examination. The aim of this study is to investigate the usefulness of visual evoked potentials (VEP) in patients with pineal gland cyst due to the possible compression on the visual pathway. SUBJECTS AND METHODS: Black-and-white pattern-reversal checkerboard VEP were recorded in 75 patients (50 females and 25 males, mean age 26.3 ± 15.7 and 25.6 ± 17.6 years, respectively) with pineal gland cyst detected on magnetic resonance of the brain (subject group) and 75 age and sex-matched control subjects (control group). Amplitudes and P100 latencies were collected and later grouped as: (1) normal finding; (2) prechiasmal; (3) prechiasmal and postchiasmal; and (4) postchiasmal dysfunction. RESULTS: P100 latencies differed significantly between subject (110.26 ± 13.23 ms) and control group (101.01 ± 5.36 ms) (p < 0.01). Findings of the VEP differed significantly (p < 0.01) between subject and control group, mainly due to the postchiasmal dysfunction frequency in subject group. Findings of the VEP differed significantly according to the pineal gland cyst volume (p = 0.006) with more frequent postchiasmal dysfunctions among subjects with larger cysts. Postchiasmal changes were significantly more frequent in patients with described compression of the cyst on surrounding brain structures (p = 0.016). CONCLUSIONS: Postchiasmal dysfunction on VEP can be seen in patients with pineal gland cyst, mostly with larger cysts and with compression of the cyst on surrounding brain structures. VEP serve as a useful method to determine functional impairment of the visual pathway in patients with pineal gland cyst.