Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent ß-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.

The Optimal Targeting for Focused Ultrasound Thalamotomy Differs between Dystonic and Essential Tremor: A 12-Month Prospective Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. OBJECTIVES: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. METHODS: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. RESULTS: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. CONCLUSIONS: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT.

Effects of osteopathic manipulative treatment of the pivots on lower limb function in young professional football players.

INTRODUCTION: The most frequent injuries in professional soccer players are those pertinent to the lower limbs. In particular, strains of the hamstrings and ligamentous injuries of the knee. Therefore, preventive measures are aimed to reduce such events. We aimed to investigate if an osteopathic manipulative treatment (OMT) of the pivots could improve lower limb function in young professional football players. METHODS: Thirty-eight young male professional football players were recruited (mean age 17.8 ± 0.44 years). These were randomly assigned to an OMT or control group (n = 20 and 18, respectively). Both groups underwent osteopathic evaluation. A sit-and-reach test, a vertical jump test, a hand-grip strength test, a cervical ROM test and a balance evaluation were also performed. RESULTS: A significant improvement (p < 0.01) was observed between pre and post measures in the OMT for dysfunctional assessment of the pivots. However, only L3 and C2 also differed from the control group post evaluation (p < 0.0001). No differences were present for any functional measure in the control group. Only the sit-&-reach of the OMT increased significantly (p < 0.001). Static balance with open eyes in the OMT, but not in the control group, improved during post evaluation (p < 0.01). CONCLUSION: The OMT of the pivots was able to increase the sit-and-reach measure, improve postural control with open eyes and improve dysfunctional patterns of the lumbosacral and upper cervical spine in young professional football players.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). OBJECTIVE: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. METHODS: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12 months after thalamotomy. RESULTS: We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. CONCLUSIONS: In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

National networking in rare diseases and reduction of cardiac burden in thalassemia major.

AIMS: A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). METHODS AND RESULTS: Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. CONCLUSION: Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients.

A pilot study on non-invasive treatment of migraine: The self-myofascial release.

The aims of this paper was to determine the effect of self-myofascial release (SMFR) on postural stability and to analyze if it can influence migraine condition. Twenty-five subjects (age 49.7± 12.5) affected by migraine were enrolled. Assessments included a stabilometric analysis in order to evaluate balance and plantar support, with eyes open (OE) and closed (CE); cervical ROM measurement; evaluation of upper limb strength through handgrip. All the analysis were carried out before and after the administration of a single SMFR protocol, using medium density small balls laid in the three most painful trigger points in migraine patients: trapezius, sternocleidomastoids and suboccipital muscles. Performing a T test for paired samples, there was a significant increase in two ranges of the stabilometric analysis: ellipse surface, both with open and closed eyes (p value EO = 0.05; p value EC = 0.04) and length of the sway path, but just with closed eyes (p value = 0.05). SMFR might have a positive impact on postural stability in subjects with migraine. Further investigation should be conducted to confirm the hypothesis.

The Close Link of Pancreatic Iron With Glucose Metabolism and With Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study.

OBJECTIVE: We systematically explored the link of pancreatic iron with glucose metabolism and with cardiac complications in a cohort of 1,079 patients with thalassemia major (TM) enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. RESEARCH DESIGN AND METHODS: MRI was used to quantify iron overload (T2* technique) and cardiac function (cine images) and to detect macroscopic myocardial fibrosis (late gadolinium enhancement technique). Glucose metabolism was assessed by the oral glucose tolerance test (OGTT). RESULTS: Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with impaired fasting glucose, impaired glucose tolerance, and diabetes. A pancreas T2* <13.07 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for disturbances of glucose metabolism and for cardiac iron. Patients with myocardial fibrosis showed significantly lower pancreas T2* values. Patients with cardiac complications had significantly lower pancreas T2* values. No patient with arrhythmias/heart failure had a normal global pancreas T2*. CONCLUSIONS: Pancreatic iron is a powerful predictor not only for glucose metabolism but also for cardiac iron and complications, supporting the close link between pancreatic iron and heart disease and the need to intensify iron chelation therapy to prevent both alterations of glucose metabolism and cardiac iron accumulation.

Deep Brain Stimulation of the Caudal Zona Incerta and Motor Thalamus for Postischemic Dystonic Tremor of the Left Upper Limb: Case Report and Review of the Literature.

BACKGROUND: Dystonic tremor is defined as a tremor occurring in a body region affected by dystonia. The pathophysiologic mechanisms behind dystonic tremor supposedly involve anomalies affecting the pallidothalamic-receiving area (for the dystonic component) and the ventralis intermedius-cortical loop (for the tremor component). Interest in posterior subthalamic area stimulation for various types of involuntary abnormal movements has arisen owing to positive results in patients affected by tremor refractory to ventralis intermedius deep brain stimulation. CASE DESCRIPTION: A 23-year-old man, with a 15-year history of left upper limb dystonic tremor due to a stroke in the right thalamus, underwent deep brain stimulation with a single electrode passing through the right ventralis oralis anterior/ventralis oralis posterior nuclei and caudal zona incerta. Objective movement outcomes were assessed through the Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor. The impact of tremor on activities of daily living was assessed with the ADL-T24 questionnaire, and quality of life was assessed with the Quality of Life Scale. All questionnaires were administered before deep brain stimulation and at 5-year follow-up. Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor scores decreased from 14.5 to 4.5 and from 46 to 7, respectively. ADL-T24 score decreased from 19 to 3, whereas Quality of Life Scale score increased from 49 to 82. CONCLUSIONS: Stimulation of motor thalamus and caudal zona incerta could be a viable treatment for patients affected by tremor of various origins, including dystonic tremor, refractory to medical therapy.

Long-term occipital nerve stimulation for drug-resistant chronic cluster headache.

Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end-point was a reduction in number of daily attacks. Results After a median follow-up of 6.1 years (range 1.6-10.7), 20 (66.7%) patients were responders (≥50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60-80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2-48 months). Battery depletion (21 patients 70%) and electrode migration (six patients - 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement.

Peripheral Nerve Field Stimulation (PNFS) as a Treatment Option for Intractable Radiation-Induced Facial Neuropathic Pain in a Survivor of Laryngeal Cancer: A Case Report.

BACKGROUND: Treatment-related chronic neuropathic pain represents a major and increasing cause of discomfort in cancer survivors. Unfortunately, in approximately 10%-15% of cases, pain is scarcely relieved by opioids and common painkillers. Thus, alternative measures to manage pain have recently been adopted in these patients. CASE DESCRIPTION: We report the case of a laryngeal cancer survivor who developed an intractable bilateral mandibular radiation-induced neuropathic pain syndrome. His pain was refractory to any pharmacological treatment, whereas the implant of bilateral subcutaneous facial electrodes led to the complete resolution of pain. CONCLUSIONS: To the best of our knowledge, this is the first report in literature describing peripheral nerve field stimulation as a treatment option for intractable cancer treatment-related chronic neuropathic pain. Peripheral nerve field stimulation appears to be a safe and effective procedure.

Surgery for treatment of refractory chronic cluster headache: toward standard procedures.

The degree of disability due to chronic cluster headache refractory to conservative treatments justifies surgical procedures as second-line treatments. Many studies and reports nowadays confirm the efficacy of the two mostly used surgical techniques in such cases. Both deep brain stimulation and occipital nerve stimulation are in fact currently utilized for this purpose but the surgical technique has not yet been standardized. We describe the surgical steps of both procedures.

Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: first reported case.

INTRODUCTION: Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface. METHODS: A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta. RESULTS: After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up. DISCUSSION: This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.

From neuroimaging to patients' bench: what we have learnt from trigemino-autonomic pain syndromes.

Trigeminal autonomic cephalalgias (TACs) are primary headaches including cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). A number of neuroimaging studies have been conducted in last decade showing involvement of brain areas included in the pain matrix. Apart from pain matrix involvement, other neuroimaging findings data deserve special attention. The hypothalamic activation reported in the course of TAC attacks coupled with the efficacy of hypothalamic neurostimulation to treat drug-resistant TAC forms clearly indicate the posterior hypothalamus as a crucial area in TAC pathophysiology. In animal models this brain area has been shown to modulate craniofacial pain; moreover, hypothalamic activation occurs in other pain conditions, suggesting that posterior hypothalamus has a more complex role in TAC pathophysiology rather than simply being considered as a trigger. In contrast, hypothalamic activation may serve as a crucial area in terminating rather than triggering attacks. It also could lead to a central condition facilitating initiation of TAC attacks.

Improvement of secondary fixed dystonia of the upper limb after chronic extradural motor cortex stimulation in 10 patients: first reported series.

BACKGROUND: Fixed dystonic postures secondary to ischemic, traumatic, or postsurgical lesions located in the basal ganglia and brainstem constitute a major therapeutic challenge and limit motor rehabilitation efficacy. They are often refractory to conservative treatment. Aberrant cerebral plasticity developed after deep brain lesions is thought to lead to abnormal cortical representation of the affected part of the body and then to pathological fixed postures. OBJECTIVE: To assess the efficacy of motor cortex stimulation in patients with upper limb fixed dystonia. METHODS: Ten patients were submitted to computer-assisted and electromyography-monitored implantation of intracranial epidural electrodes over the central cortical sulcus contralateral to the affected limb. Patients were followed up from 1 to 9 years (9 patients), except for patient 10, whose follow-up was limited to 4 months. RESULTS: Seven of 7 patients showed > 30% improvement in the Disability of Shoulder, Arm, and Hand Scale and an overall 70% increase in the score of the Short Form-36 Physical Activity subscale with significant and stable improvement of quality of life during stimulation. The partial recovery of hand dexterity observed in most of the treated patients additionally contributed to a significant improvement of their quality of life. CONCLUSION: Although the pathophysiology of fixed dystonia is unknown, our results suggest a major role of the motor cortex in this condition and reinforce the hypothesis that postlesional delayed cortical rearrangements might take place in these forms and be the target of effective therapeutic neuromodulation.

Spinal cord stimulation for recurrent painful neuromas of the foot.

The authors report the case of a patient affected by recurrent neuromas of the interdigital nerves of the left foot that appeared after surgery for Morton's disease. Implantation of spinal cord stimulation (SCS) system was performed after three unsuccessful surgical revisions, which demonstrated the presence of multiple neuromas growing at endings of the stumps of the nerves and fasciculi. The patient developed chronic neuropathic pain localized within the third metatarsal region of the left foot. Conservative treatments failed and autonomous gait became impossible. SCS immediately abolished pain and the patient was able to perform her normal daily activities within 1 month. At our knowledge, this is the first report in literature of SCS successfully employed for recurrent and refractory pain due to Morton's neuroma.

Neuromodulation for refractory headaches.

Drug refractory headaches constitute an important cause of social life disability; when a lack of responsiveness to conservative treatments is ascertained for these pathological conditions, surgical options are considered. Several lines of evidence exist to assert that the neuromodulation procedures available so far are safe and effective in a large amount of patients for the treatment of different types of severe primary and secondary headaches. Central (deep-brain stimulation, DBS) and peripheral [vagus nerve stimulation (VNS), occipital nerve stimulation (ONS), subcutaneous trigeminal stimulation] neuromodulation procedures are here reviewed as reported in literature along with the experience of our Institute.

Occipital nerve stimulation (ONS). Surgical technique and prevention of late electrode migration.

Occipital nerve stimulation (ONS) is an emerging procedure for the treatment of cranio-facial pain syndromes and headaches refractory to conservative treatments. The aim of this report is to describe in detail the surgical intervention and to introduce some useful tricks that help to avoid late displacement and migration of the suboccipital leads. The careful description of the surgical steps may contribute to a standardization of the procedure and make the interpretation of results easier even if obtained in series of patients operated on by different authors.

Wernicke's encephalopathy after allogeneic stem cell transplantation.

Wernicke's encephalopathy is an acute neuropsychiatric condition due to thiamine deficiency frequently associated with chronic alcohol abuse. We describe 2 cases of patients who experienced acute Wernicke's encephalopathy after allogeneic stem cell transplantation associated with the use of commercial total parental nutrition. Early diagnosis with magnetic resonance imaging and timely treatment with thiamine resulted in rapid resolution of clinical and radiological signs. In conclusion, the prolonged use of commercial total parental nutrition formulas must be supplemented with thiamine in the form of intramuscularly administered multivitamins.