Idiopathic cervical dystonia and non-motor symptoms: a pilot case-control study on autonomic nervous system.

PURPOSE: Non-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature. METHODS: We conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio. RESULTS: ICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing. CONCLUSION: ICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations.

Reversible cerebral vasoconstriction syndrome: strategies to early diagnosis and the role of transcranial color-coded doppler ultrasonography (TCCD).

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a cerebrovascular transitory condition characterized by severe headache, possible concomitant acute neurological symptoms, evidence of diffuse multifocal segmental constriction of cerebral arteries, and usually spontaneously resolving within 3 months. Putative causes and/or precipitating factors are vasoactive drugs-e.g., antidepressants, α-sympathomimetics, triptans-post-partum, and immunosuppressants. CASE PRESENTATION: We report the case of a middle-aged woman referred to the emergency room (ER) with a 7-day long intense headache and vomit. Cerebral non-contrast computed tomography (CT) was negative for acute ischemic lesions or intracranial bleedings. She was again referred to ER 7 days later with additional fluctuating episodes of weakness in left arm and both lower limbs. A new brain CT was negative. Due to worsening headache, a transcranial color-coded Doppler (TCCD) was performed, which showed diffuse multifocal blood flow acceleration in all principal intracranial vessels, and particularly on the right hemisphere. These findings were subsequently confirmed at MR angiogram and digital subtraction angiography. CONCLUSION: TCCD imaging is a non-invasive and relatively inexpensive tool which provides real-time information on cerebrovascular function, blood flow velocities, and hemodynamic changes. TCCD may be a powerful tool in the early detection of acute infrequent cerebrovascular conditions, as well as in monitoring their course and the therapeutic response.

TeleNEwCARe: An Italian case-control telegenetics study in patients with Hereditary NEuromuscular and CARdiac diseases.

Telemedicine provides healthcare services remotely and represents a fundamental resource for the management of rare and fragile patients. Tele-health implementation is a main objective of the European Reference Networks (ERNs) mission to accelerate diagnosis for rare diseases. TeleNewCARe is a pilot case-control project which evaluates the efficacy and satisfaction of telegenetics for neuromuscular and cardiac adult patients, compared to face-to-face genetic counselling. The virtual sessions were co-hosted by a medical geneticist and a neurologist/cardiologist. Specific questionnaires (Clinical Genetics Satisfaction Questionnaire (CGS), Telemedicine Satisfaction Questionnaire (TSQ) and a Satisfaction Questionnaire for medical geneticists) were used to assess the effectiveness and fulfilment of telecounselling, both for patients and health care providers. Satisfaction expressed for telegenetics did not significantly differ from face-to-face counselling. The virtually enrolled patients declared they had the possibility to relate confidentially with the specialists, to share information and to be informed in an exhaustive way about their disease. Almost all patients declared themselves willing to reuse the telecounselling in the future. The multidisciplinary care was perceived as a significant added value. No overt technical problems were reported although the need for digital skills and tools can limit patients' compliance. Our experience supports telegenetics as a valid alternative to traditional genetic counselling in cardiac and neuromuscular patients. This innovative approach facilitates multidisciplinary care, grants a periodical follow up, without forcing patients to discomfortable travelling, and allows to maintain expert care. This result meets the ERNs needs to reduce patients' burden to access and monitor their healthcare.

Pediatric recurrent acute necrotizing encephalomyelitis, RANBP2 genotype and Sars-CoV-2 infection: Diagnosis, pathogenesis and targeted treatments from a case study.

Acute necrotizing encephalopathy (ANE) is a rare disease not yet described in children with Covid-19. RANBP2 gene variations are implicated in recurrences in the genetic form of ANE, the so called ANE1. We report the first case of pediatric ANE1 following Sars-CoV-2 infection. She had a first episode at 2 years of age following influenza type A with full recovery, many other respiratory and non-respiratory febrile viral infections without recurrences and a severe recurrence following Sars-CoV-2 infection, suggesting a potentiation effect on cytokine cascade. Her MRI showed the typical pattern of injury resembling that of mitochondrial disorders, and supported the role of RANBP2 in mitochondrial homeostasis. This case rises attention on diagnostic challenges and offers several interesting tips for discussion about new perspectives in pathogenesis and targeted treatments.

Electrophysiological and neuropsychological assessment of cognition in spinocerebellar ataxia type 1 patients: a pilot study.

BACKGROUND: Event-related potentials (ERPs) reflect cognitive processing: negative early components (N100, N200) are involved in the sensory and perceptual processing of a stimulus, whereas late positive component P300 requires conscious attention. Both neuropsychological and affective disorders are present in patients with spinocerebellar ataxia type 1 (SCA1), but the underlying mechanisms need further clarification. MATERIALS AND METHODS: In this pilot study, we assessed cognitive processing by recording auditory ERPs in 16 consecutive SCA1 patients and 16 healthy controls (HC) matched for age and sex. Motor and nonmotor symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) and an extensive neuropsychological battery. ERPs were recorded using an oddball paradigm, and peak latency and amplitude of N100, N200, and P300 were measured in the averaged responses to target tones. RESULTS: We found in SCA1 significantly increased latencies of N200 and P300 (p=0.033, p=0.007) and decreased amplitudes of N100 and P300 (p=0.024, p=0.038) compared with HC. Furthermore, P300 latency had the highest AUC in the discrimination of SCA1 in ROC analysis. The expansion of trinucleotide repeats correlated with P300 latency (r=-0.607, p=0.048), whereas both P300 and N100 amplitudes correlated with the severity of motor symptoms (r=-0.692, p=0.003; r=-0.621; p=0.010). Significant correlations between P300 latency and the scores of Emotion Attribution Task (r=-0.633, p=0.027), as well as between N200 latency and the scores of Frontal Assessment Battery and Stroop test (r=-0.520, p=0.047; r=0.538, p=0.039), were observed. CONCLUSIONS: This research provides for the first time an extensive characterization of ERPs as useful electrophysiological markers to identify early cognitive dysfunction in SCA1.

Suppressing gain-of-function proteins via CRISPR/Cas9 system in SCA1 cells.

SCAs are autosomal dominant neurodegenerative disorders caused by a gain-of-function protein with toxic activities, containing an expanded polyQ tract in the coding region. There are no treatments available to delay the onset, stop or slow down the progression of these pathologies. In this work we focus our attention on SCA1 which is one of the most common genotypes circulating in Italy. Here, we develop a CRISPR/Cas9-based approach to reduce both forms of the ATXN1 protein, normal and mutated with expanded polyQ. We started with the screening of 10 different sgRNAs able to target Exon 8 of the ATXN1 gene. The two most promising sgRNAs were validated in fibroblasts isolated from SCA1 patients, following the identification of the best transfection method for this type of cell. Our silencing approach significantly downregulated the expression of ataxin1, due to large deletions and the introduction of small changes in the ATXN1 gene, evidenced by NGS analysis, without major effects on cell viability. Furthermore, very few significant guide RNA-dependent off-target effects were observed. These preliminary results not only allowed us to identify the best transfection method for SCA1 fibroblasts, but strongly support CRISPR/Cas9 as a promising approach for the treatment of expanded polyQ diseases. Further investigations will be needed to verify the efficacy of our silencing system in SCA1 neurons and animal models.

Case Report: A Case of Creutzfeldt-Jakob Heidenhain Variant Simulating PRES.

The Heidenhain Variant of Creutzfeldt-Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical-instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD.

Trans-anal irrigation in patients with multiple sclerosis: Efficacy in treating disease-related bowel dysfunctions and impact on the gut microbiota: A monocentric prospective study.

Background: Constipation and faecal incontinence are not so uncommon in patients with multiple sclerosis, impairing quality of life. The gut microbiota is altered in multiple sclerosis patients and likely contributes to disease pathogenesis. Trans-anal irrigation has been proven to allow treatment of neurogenic bowel dysfunction and may affect gut microbiota. Objectives: The primary outcome was trans-anal irrigation effectiveness on constipation and faecal incontinence. The secondary outcome was gut microbiota profiling compared to healthy subjects and during trans-anal irrigation adoption. Methods: We conducted a prospective cohort study on multiple sclerosis patients, screened with Patient Assessment of Constipation Quality of Life questionnaire before undergoing constipation and faecal incontinence scoring, abdomen X-ray for intestinal transit time, compilation of food and evacuation diaries and faecal sample collection for gut microbiota analysis before and after 4 weeks of trans-anal irrigation. Results and Conclusions: Eighty patients were screened of which nearly half had intestinal symptoms. The included population (n = 37) was predominantly composed of women with significantly longer disease duration, higher mean age and disability than the excluded one (p < 0.05). Twelve patients completed the trans-anal irrigation phase, which led to significant improvement of bowel dysfunction symptom-related quality of life, increase in gut microbiota diversity and reduction of the proportions of pro-inflammatory taxa (p < 0.05). Trans-anal irrigation was safe, satisfactory and could help counteract multiple sclerosis-related dysbiosis.

Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy.

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype-phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70-75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype-genotype correlations in the ALS population of ERR.

Mitofusin 2: The missing link between mtDNA maintenance defects and neurotransmitter disorders.

Mitofusin (MFN) 2 belongs to the large family of mitochondrial transmembrane GTPases and has a role in dynamic mitochondrial remodeling process governed by fusion and fission. MFN2 pathogenic variants classically cause Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of CMT, but patients with complex and unusual phenotypes involving the central and peripheral nervous system have been described, with mitochondrial dysfunction proposed as the underlying pathogenic mechanism. Here, we report the first description of a neurochemical pattern of secondary alterations in the metabolism of biogenic amines linked to the de novo presence of the hotspot MFN2 pathogenic variant p.Arg104Trp. The infant presented a very early onset choreic movement disorder associated with severe axial hypotonia and fluctuating dystonia of limbs. The relationship between mitochondrial DNA (mtDNA) maintenance defects and dopaminergic neurotransmitter disorders, governed by MFN2, is discussed.

The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.

Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 months were randomly assigned in a 1:1:1:1 ratio to receive 64 mg, 32 mg or 16 mg of guanabenz or placebo daily for 6 months as an add-on therapy to riluzole. The purpose of the placebo group blinding was to determine safety but not efficacy. The primary outcome was the proportion of patients progressing to higher stages of disease within 6 months as measured using the ALS Milano-Torino staging system, compared with a historical cohort of 200 patients with ALS. The secondary outcomes were the rate of decline in the total revised ALS functional rating scale score, slow vital capacity change, time to death, tracheotomy or permanent ventilation and serum light neurofilament level at 6 months. The primary assessment of efficacy was performed using intention-to-treat analysis. The treatment arms using 64 mg and 32 mg guanabenz, both alone and combined, reached the primary hypothesis of non-futility, with the proportions of patients who progressed to higher stages of disease at 6 months being significantly lower than that expected under the hypothesis of non-futility and a significantly lower difference in the median rate of change in the total revised ALS functional rating scale score. This effect was driven by patients with bulbar onset, none of whom (0/18) progressed to a higher stage of disease at 6 months compared with those on 16 mg guanabenz (4/8; 50%), the historical cohort alone (21/49; 43%; P = 0.001) or plus placebo (25/60; 42%; P = 0.001). The proportion of patients who experienced at least one adverse event was higher in any guanabenz arm than in the placebo arm, with higher dosing arms having a significantly higher proportion of drug-related side effects and the 64 mg arm a significantly higher drop-out rate. The number of serious adverse events did not significantly differ between the guanabenz arms and the placebo. Our findings indicate that a larger trial with a molecule targeting the unfolded protein response pathway without the alpha-2 adrenergic related side-effect profile of guanabenz is warranted.

Report of a novel ATP7A mutation causing distal motor neuropathy.

We describe a novel ATP7A gene mutation associated with distal motor neuropathy, mild connective tissue abnormalities and autonomic disturbances. Next-generation sequencing analysis of a lower-motor neuron diseases gene panel was performed in two sibs presenting with distal motor neuropathy plus an autonomic dysfunction, which main manifestations were retrograde ejaculation, diarrhea and hyperhydrosis. Probands underwent dysmorphological, neurological, electrophysiological as well as biochemical evaluations and somatic and autonomic innervation studies on skin biopsies. A novel missense mutation (p.A991D) was identified in the X-linked ATP7A gene, segregating in both brothers and inherited from their healthy mother. Biochemical studies on patients' blood samples showed reduced serum copper and ceruloplasmin levels. Clinical and neurophysiological evaluation documented dysautonomic signs. Quantitative evaluation of skin innervation disclosed a small fiber neuropathy with prevalent autonomic involvement. Mutations in the ATP7A gene, encoding for a copper-transporting ATPase, have been associated with the severe infantile neurodegenerative Menkes disease and in its milder variant, the Occipital Horn Syndrome. Only two ATP7A mutations were previously reported as causing, a pure axonal distal motor neuropathy (dHMN-SMAX3). The phenotype we report represents a further example of this rare genotype-phenotype correlation and highlights the possible occurrence in SMAX3 of autonomic disturbances, as described for Menkes disease and Occipital Horn Syndrome.

Is Peripheral Oxygen Saturation a Reliable Predictor of Upper Airways Air-Flow Limitation?

BACKGROUND: Dyspnea secondary to acute upper airways airflow limitation (UAAFL) represents a clinical emergency that can be difficult to recognize without a suitable history; even when etiology is known, parameters to assess the severity are unclear and often improperly used. OBJECTIVES: The aim of this study was to assess the role of peripheral oxygen saturation (SpO2) as a predictor of severity of upper airway obstruction. METHODS: The authors propose an experimental model of upper airway obstruction by a progressive increase of UAAFL. Ten healthy volunteers randomly underwent ventilation for 6 min with different degrees of UAAFL. SpO2, heart rate, respiratory rate (RR), tidal volume, accessory respiratory muscle activation, and subjective dyspnea indexes were measured. RESULTS: In this model, SpO2 was not reliable as the untimely gravity index of UAAFL. Respiratory rate, visual analogue scale (VAS), and Borg dyspnea scale were statistically correlated with UAAFL (p < 0.0001 for RR and p < 0.05 for VAS and Borg scale). No significant changes were observed on heart rate (p > 0.05) and tidal volume (p > 0.05); a RR ≤ 7 breaths/min; VAS and Borg scale showed statistically significant parameters changes (p < 0.05). CONCLUSIONS: RR, VAS, and Borg dyspnea scales are sensitive parameters to detect and stage, easily and quickly, the gravity of an upper airways impairment, and should be used in emergency settings for an early diagnosis of a UAAFL. SpO2 is a poorer predictor of the degree of upper airways flow limitation.

A cross-sectional study investigating frequency and features of definitely diagnosed diabetic painful polyneuropathy.

This cross-sectional multicentre study aimed at investigating frequency and features of painful diabetic polyneuropathy. We consecutively enrolled 816 patients attending hospital diabetic outpatient clinics. We first definitely diagnosed diabetic polyneuropathy and pure small-fibre polyneuropathy using clinical examination, nerve conduction study, and skin biopsy or quantitative sensory testing. Adhering to widely agreed criteria, we then identified neuropathic pain and diagnosed painful polyneuropathy using a combined approach of clinical examination and diagnostic tests. Of the 816 patients, 36% had a diabetic polyneuropathy associated with male sex, age, and diabetes severity; 2.5% of patients had a pure small-fibre polyneuropathy, unrelated to demographic variables and diabetes severity. Of the 816 patients, 115 (13%) suffered from a painful polyneuropathy, with female sex as the only risk factor for suffering from painful polyneuropathy. In this large study, providing a definite diagnosis of diabetic polyneuropathy and pure small-fibre polyneuropathy, we show the frequency of painful polyneuropathy and demonstrate that this difficult-to-treat complication is more common in women than in men.

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials.

Background. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established. MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration. Methods. 19 MS patients underwent clinical examination, numerical rating scale (NRS), quantitative sensory testing (QST), and laser-evoked potentials (LEPs) before and after 1 month of therapy. Psychophysiological and neurophysiological data were compared to sex- and age-matched controls. Results. Patients reported a significant reduction in pain. We found statistically significant differences in LEP parameters between patients and controls but no significant change in LEP measures after THC/CBD therapy. Cold and heat detection thresholds were altered in patients but did not change after THC/CBD therapy. There was a significant increase in cold pain threshold by hand stimulation and a significant reduction in abnormal cold perception thresholds. Conclusions. Our results indicate that Sativex® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels.

Interventional treatment for neuropathic pain due to combined cervical radiculopathy and carpal tunnel syndrome: a case report.

The coexistence of median and cervical nerve root damage might hide a complex pathophysiology. Here, we describe and discuss the case of a patient suffering from numbness and painful tingling of the hand, whose symptoms were effectively treated with pulsed radiofrequency and epidural administration of bupivacaine and morphine.

Diagnosing and assessing pain in neurorehabilitation: from translational research to the clinical setting. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Pain is very common in neurorehabilitation, where it may be a target for treatment and have a negative effect on rehabilitation procedures and outcomes. Promising preliminary preclinical data support certain therapeutic approaches to pain, but there is a strong need of adequate preclinical models, experimental settings, outcome measures, and biomarkers that are more relevant for pain within the neurorehabilitation field. Data on the diagnosis and assessment of nociceptive and neuropathic pain (NP) are very scanty in neurorehabilitation, but those from other contexts can be adapted and translated to this specific setting. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has searched and evaluated existing evidence on animal models for the treatment of pain, definition and diagnostic criteria for nociceptive and NP, screening tools and questionnaires, along with diagnostic, clinical and instrumental techniques to distinguish nociceptive from NP and, more generally, to assess pain in the field of neurorehabilitation. The present ICCPN recommendations provide information on the relevance of current preclinical models, and may be helpful in ameliorating pain diagnosis and assessment, which are prerequisites for better application and tailoring of current pharmacological and non-pharmacological treatments. They may also be useful for future studies aimed at filling the gaps in the current knowledge of these topics.

The course and the anatomo-functional relationships of the optic radiation: a combined study with 'post mortem' dissections and 'in vivo' direct electrical mapping.

Even if different dissection, tractographic and connectivity studies provided pure anatomical evidences about the optic radiations (ORs), descriptions of both the anatomical structure and the anatomo-functional relationships of the ORs with the adjacent bundles were not reported. We propose a detailed anatomical and functional study with 'post mortem' dissections and 'in vivo' direct electrical stimulation (DES) of the OR, demonstrating also the relationships with the adjacent eloquent bundles in a neurosurgical 'connectomic' perspective. Six human hemispheres (three left, three right) were dissected after a modified Klingler's preparation. The anatomy of the white matter was analysed according to systematic and topographical surgical perspectives. The anatomical results were correlated to the functional responses collected during three resections of tumours guided by cortico-subcortical DES during awake procedures. We identified two groups of fibres forming the OR. The superior component runs along the lateral wall of the occipital horn, the trigone and the supero-medial wall of the temporal horn. The inferior component covers inferiorly the occipital horn and the trigone, the lateral wall of the temporal horn and arches antero-medially to form the Meyer's Loop. The inferior fronto-occipital fascicle (IFOF) covers completely the superior OR along its entire course, as confirmed by the subcortical DES. The inferior longitudinal fascicle runs in a postero-anterior and inferior direction, covering the superior OR posteriorly and the inferior OR anteriorly. The IFOF identification allows the preservation of the superior OR in the anterior temporal resection, avoiding post-operative complete hemianopia. The identification of the superior OR during the posterior temporal, inferior parietal and occipital resections leads to the preservation of the IFOF and of the eloquent functions it subserves. The accurate knowledge of the OR course and the relationships with the adjacent bundles is crucial to optimize quality of resection and functional outcome.

Acute respiratory failure onset in a patient with Guillain-Barré syndrome after Legionella-associated pneumonia: a case report.

A 69-year-old white man was admitted because of a clinical history of persistent cough and fever. Chest x-rays showed bilateral lung infiltrates with air bronchograms, whereas the urine antigen test resulted positive for Legionella pneumophila. The next day, he was transferred to the intensive care unit and intubated because of severe renal and respiratory distress. Neurological examination revealed distal weakness and loss of deep tendon reflexes in lower extremities. Nerve conduction studies displayed severe demyelinating sensorimotor polyneuropathy, and plasmapheresis was therefore applied with mild improvement. Few weeks after, dysphagia occurred and electrophysiologic tests showed progressive axonal involvement with spread of demyelination to the cranial nerves. The patient underwent a new plasmapheresis course and slowly reached stable clinical improvement of neurological status, which allowed him to be safely discharged. This case showed a critical onset with respiratory failure and kidney functional impairment due to L. pneumophila, subsequently disclosing Guillain-Barré syndrome.