Persistent hemiplegia with normal intraoperative neurophysiological monitoring in supratentorial neurosurgery: a case report and review of literature.

Intraoperative neurophysiological monitoring (IONM) is needed for evaluating and demonstrating the integrity of the central and peripheral nervous system during surgical manoeuvres that take place in proximity to eloquent motor and somatosensory nervous structures. The integrity of the monitored motor pathways is not always followed by consistent clinical normality, particularly in the first hours/days following surgery, when surgical resection involves brain structures such as the supplementary motor areas (SMA). We report the case of a patient who underwent surgical excision of a right frontal glioblastoma with normal preoperative, intraoperative (IONM), and postoperative central motor conduction, but with persistent postoperative hemiplegia (> 6 months). The literature regarding SMA syndrome and its diagnosis and prognosis is reviewed.

The D.A.M.A. Project at Terni Hospital, Italy.

Experience shows how difficult it is for a person with disabilities to cope with the reality of a hospital, especially if he or she has an intellectual disability. The difficulty in carrying out even simple diagnostic and therapeutic manoeuvres, the complexity of the pathologies, the difficulty in relating to the patient all make it a real risk that many medical problems of patients with disabilities are overlooked or denied altogether. The person with a disability has the right to all care, not only that related to his or her particular pathology, but also that required for other specialist or general pathologies. The UN Convention clearly states the rights of persons with disabilities. The Italian Republic has implemented the UN's declaration with Law 18/2009. The rights enshrined in Article 25 of the UN Convention are also concretely applied in the European Charter of Patients' Rights. The right of people with disabilities to be treated on an equal and non-discriminatory basis is also recalled by His Holiness Pope Francis in his latest encyclical. The DAMA (Disabled Advanced Medical Assistance) Hospital project was created to guarantee the right to health and care of people with disabilities, always, by remodelling its diagnostic and care procedures. The CAD/DAMA Service of the Terni Hospital since 2018 has adopted the DAMA project and also since 2018 has been collaborating with the Seraficio Institute of Assisi. The aim of the CAD/DAMA Service is also to promote and implement research in this area of care and training for healthcare professionals on disability and related issues.

The Effect of Mozart's Music in Severe Epilepsy: Functional and Morphological Features.

Music is a very important factor in everyday life, involving mood, emotions and memories. The effect of music on the brain is very debated. Certainly, music activates a complex network of neurones in auditory areas, mesolimbic areas, cerebellum and multisensory areas. In particular, music exerts its effects on the brain of patients with epilepsy, having a dichotomous influence: it can either be seizure-promoting in musicogenic epilepsy or antiepileptic. Several studies have shown that seizure-prone neural networks may be stimulated by certain periodicities while other frequencies may prevent seizure activity. There are a lot of data in the literature about the so-called "Mozart effect" (Rauscher et al. 1993). In previous studies we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of the cases. In this study we are conducting a survey on the observation of what happens to the brain of patients suffering from drug-resistant epilepsy through electroencephalographic investigations, brain MRI and behavioural analysis before and after six months of listening to Mozart music (Sonata K.448). The first step is to present the data of the first patient under investigation.

Mozart's music and multidrug-resistant epilepsy: a potential EEG index of therapeutic effectiveness.

Multidrug-resistant epilepsy is a pathological condition that affects approximately one-third of patients with epilepsy, especially those with associated intellectual disabilities. Several non-pharmacological interventions have been proposed to improve quality of life of these patients. In particular, Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal electroencephalography (EEG) discharges and recurrence of clinical seizures in these patients. In a previous study we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of cases. This study aims to assess electroencephalography as a quantitative (qEEG) predictive biomarker of effectiveness of listening to music on the frequency of epileptic discharges and on background rhythm frequency (BRF).

Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis.

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.

A Combined One-Staged Robot-Assisted Sacral Chordoma Resection.

BACKGROUND: The robotic surgery is an advanced modern minimally invasive technology, widely used in urologic oncology, and it has become useful in particular conditions. Over time, different surgical specialties made use of the robotic properties to minimize complications for high-risk procedures. A combined 1-staged robot-assisted multidisciplinary surgery with intraoperative neurophysiological monitoring can be a safe procedure to remove a sacral chordoma with low morbidity rates. CASE DESCRIPTION: A 64-year-old woman complained of a few months of drug-resistant low back and abdominal pain. The subsequent development of constipation brought the patient to undergo an abdominal computed tomography scan and magnetic resonance imaging. Radiologic investigations revealed a large size sacral mass associated with a partial destruction of the sacrum and posterior compression of the rectum. The tumor was en bloc removed by a combined 1-staged anterior laparoscopic robot-assisted and posterior open lumbosacral approach with continue intraoperative neurophysiological monitoring of sacral and pudendal plexuses. The histological diagnosis was of chordoma. After surgery, the patient reported pain relief and the total recovery of bowel dysfunction with good 11-month follow-up outcome. CONCLUSIONS: This combined technique represents a promising treatment option in selected cases. The robotic technology combined with the experience of highly qualified staff can improve the surgical result by minimizing complications. However, longer follow-up is necessary to confirm the long-term effects in terms of recurrence and survival.

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome.

The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019;8:887&897.

A 7 Mb duplication at 22q13 in a girl with bipolar disorder and hippocampal malformation.

We identified a duplication of 22q13.1-q13.2 in a 10-year-old girl and demonstrated that this duplication was the recombinant product of a maternal intrachromosomal insertion. Phenotypic characteristics included prominent forehead, small low-set ears, hypertelorism, epicanthal folds, small palpebral fissures, short philtrum, and syndactyly. MRI of the brain revealed high signal abnormalities in the periventricular white matter, a hypoplastic corpus callosum, under-rotated hippocampus on the left and atrophic hippocampus on the right. Since age 5, the child's behavior has shown cyclic maniacal episodes with severely disorganized mood and behavior. Psychiatric and cognitive assessment led to a diagnosis of bipolar disorder not otherwise specified, manic episodes, attention deficit hyperactivity disorder and moderate mental retardation. Array-CGH revealed an interstitial duplication of 6.9 Mb at chromosome 22q: dup(22)(q13.1q13.2). FISH using BAC clones confirmed the array-CGH results and demonstrated that the duplication was inverted. G-banding analysis in the proposita's mother revealed a banding pattern suggestive of an intrachromosomal insertion, as demonstrated by dual-color FISH with BACs that were duplicated in the proposita and multicolor-banding (MCB) based on microdissection derived region-specific libraries for chromosome 22. Our findings suggest that in both seemingly de novo deletions and duplications, the parent transmitting the imbalance should be investigated for possible balanced rearrangements. This report reinforces previous evidence that chromosome imbalances, and thus gene dosage effects, may be at the basis of some psychiatric disorders. Stringent correlations between submicroscopic imbalances, specific behavioral phenotypes and brain imaging will possibly help in dissecting complex behavioral traits.

Complexity of motor sequences and cortical reorganization in Parkinson's disease: a functional MRI study.

Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction.

A functional MRI study of language disturbances in subjects with migraine headache during treatment with topiramate.

Topiramate (TPM) is a new antiepileptic drug approved for the prevention of migraine headache. However its use is limited by treatment-emergent adverse events; in particular, therapy can exert profound impact on language function. In this investigation, we used functional magnetic resonance imaging (fMRI) to study the anatomofunctional correlates of language disturbances in TPM patients experiencing subjective cognitive impairment. Ten right-handed individuals receiving therapy (five with and five without language disfluency) and five matched healthy control subjects took part in this study. During fMRI subjects alternately rested and performed a word-generating task. The task comprised the silent generation of words beginning with a different input letter visually presented. The activation paradigm consisted of six activation blocks alternating with six baseline rest blocks. The main fMRI measure was the pattern activation of the prefrontal regions (Brodmann's areas 44, 45, and 46) in both left and right hemispheres. Patients receiving TPM (50-100 mg/day) significantly reduced mean monthly migraine frequency. However several differences in fMRI activation were evident in the subject group comparison. Notably, changes in brain activity were observed during the phonemic task in patients with language disturbances. It is likely that TPM therapy is associated with a "remapping" of the language cerebral network.