Cardiovascular diseases may play a negative role in the prognosis of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Only a few studies have considered the role of comorbidities in the prognosis of amyotrophic lateral sclerosis (ALS) and have provided conflicting results. METHODS: Our multicentre, retrospective study included patients diagnosed from 1 January 2009 to 31 December 2013 in 13 referral centres for ALS located in 10 Italian regions. Neurologists at these centres collected a detailed phenotypic profile and follow-up data until death in an electronic database. Comorbidities at diagnosis were recorded by main categories and single medical diagnosis, with the aim of investigating their role in ALS prognosis. RESULTS: A total of 2354 incident cases were collected, with a median survival time from onset to death/tracheostomy of 43 months. According to univariate analysis, together with well-known clinical prognostic factors (age at onset, diagnostic delay, site of onset, phenotype, Revised El Escorial Criteria and body mass index at diagnosis), the presence of dementia, hypertension, heart disease, chronic obstructive pulmonary disease, haematological and psychiatric diseases was associated with worse survival. In multivariate analysis, age at onset, diagnostic delay, phenotypes, body mass index at diagnosis, Revised El Escorial Criteria, dementia, hypertension, heart diseases (atrial fibrillation and heart failure) and haematological diseases (disorders of thrombosis and haemostasis) were independent prognostic factors of survival in ALS. CONCLUSIONS: Our large, multicentre study demonstrated that, together with the known clinical factors that are known to be prognostic for ALS survival, hypertension and heart diseases (i.e. atrial fibrillation and heart failure) as well as haematological diseases are independently associated with a shorter survival. Our findings suggest some mechanisms that are possibly involved in disease progression, giving new interesting clues that may be of value for clinical practice and ALS comorbidity management.

Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

AIMS: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. METHODS: TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). RESULTS: TDP-43 cytoplasmic accumulation was found (P < 0.05 vs. controls) in CLM of patients with mutant TARDBP or VCP, but not FUS, in line with TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. CONCLUSIONS: In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments.

Amyotrophic lateral sclerosis: a comparison of two staging systems in a population-based study.

BACKGROUND AND PURPOSE: To compare two recently developed staging systems for amyotrophic lateral sclerosis (ALS) [King's College and Milano-Torino staging (MITOS) systems] in an incident, population-based cohort of patients with ALS. METHODS: Since 2009, a prospective registry has been recording all incident cases of ALS in the Emilia Romagna region in Italy. For each patient, detailed clinical information, including the ALS functional rating scale score, is collected at each follow-up. RESULTS: Our study on 545 incident cases confirmed that King's College stages occurred at predictable times and were quite evenly spaced out throughout the disease course (occurring at approximately 40%, 60% and 80% of the disease course), whereas MITOS stages were mostly skewed towards later phases of the disease. In the King's College system there was a decrease in survival and an increase in deaths with escalating stages, whereas in the MITOS system survival curves pertaining to intermediate stages overlapped and the number of deaths was fairly homogenous throughout most stages. CONCLUSIONS: The King's College staging system had a higher homogeneity (i.e. smaller differences in survival among patients in the same stage) and a higher discriminatory ability (i.e. greater differences in survival among patients in different stages), being more suitable for individualized prognosis and for measuring efficacy of therapeutic interventions.

The prevention of neural complications in the surgical treatment of scoliosis: the role of the neurophysiological intraoperative monitoring.

Iatrogenic spinal cord injury is the most feared complication of scoliosis surgery. The importance of combined somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) monitoring during spine surgery is well known. The current authors retrospectively evaluated the results of neurophysiological intraoperative monitoring (IOM) in a large population of patients who underwent surgical treatment for spinal deformity. Intraoperative monitoring of SEPs and transcranial electrical stimulation MEPs (TES-MEP) was performed in 172 successive patients who underwent surgical treatment of idiopathic (128 pts), congenital (15 pts) or syndromic (29 pts) scoliosis. The first 106 patients (Group 1) underwent only SEP monitoring, while the other 66 patients (Group 2) underwent combined SEP and TES-MEP monitoring, when the technique was introduced in the current authors' institution. Halogenate anaesthesia (Sevoflurane, MAC 0.6-1.2) was performed in Group 1 cases, total intravenous anaesthesia (Propofol infusion, 6-10 mg/kg/h) in Group 2 patients. A neurophysiological "alert" was defined as a reduction in amplitude (unilateral or bilateral) of at least 50% for SEPs and of 65% for TES-MEPs compared with baseline. In Group 1, two patients (1.9%) developed postoperative neurologic deficits following surgical correction of spinal deformity, consisting of permanent paraparesis in one case and transient paraparesis secondary to spinal cord ischaemia in the other. Twelve patients presented intraoperative significant changes of neurophysiological parameters that improved following corrective actions by surgeons and anaesthesiologists, and did not show any postoperative neurologic deficits. In ten cases the alert was apparently unrelated to surgical manoeuvres or to pharmacological interventions and no postoperative neurologic deficits were noted. Considering the patients of Group 2, two patients (3.0%) presented transient postoperative neurologic deficits preceded by significant intraoperative changes in SEPs and TES-MEPs. In five cases a transient reduction in the amplitudes of SEPs (1 patient) and/or TES-MEPs (5 patients) was recorded intraoperatively with no postoperative neurologic deficits. In conclusion, in the current series of 172 patients the overall prevalence of postoperative neurologic deficit was 2.3% (4 patients). When combined SEP and TES-MEP monitoring was performed, the sensitivity and specificity of IOM for sensory-motor impairment was 100 and 98%, respectively. Combined SEP and TES-MEP monitoring must be regarded as the neurophysiological standard for intraoperative detection of emerging spinal cord injury during corrective spinal deformity surgery. Early detection affords the surgical team an opportunity to perform rapid intervention to prevent injury progression or possibly to reverse impending neurologic sequelae.

Chronic cerebro-spinal venous insufficiency: report of transcranial magnetic stimulation follow-up study in a patient with multiple sclerosis.

The pyramidal pathway is frequently affected early on in multiple sclerosis (MS) and impaired motor performance is a major cause of disability. Pyramidal tract function can be assessed using transcranial magnetic stimulation (TMS). TMS supports the diagnosis of MS, detecting corticospinal tract involvement and monitoring its course with or without treatment. It has been never investigated whether any relationship exists between the TMS outcome measure and minimally invasive treatment of multiple severe extracranial stenosis, affecting the principal ce rebrospinal venous segments in MS patients. We report the clinical and transcranial magnetic stimulation follow-up of a patient during a relapse in relapsing-remitting MS. She underwent percutaneous balloon angioplasty of the associated chronic cerebrospinal venous insufficiency (CCSVI), due to membranous obstruction of the proximal azygous vein, with severe stenosis of the left internal jugular vein. Treatment of the associated CCSVI made a parallel improvement in both clinical and neurophysiological parameters, allowing us to avoid high dose steroid therapy. The relationship between the clinical and neurophysiological course on the one hand, and haemodynamic correction of the associated CCSVI on the other, calls for further exploration on a wider number of patients. The impact of CCSVI on the different neuro-physiological parameters has not been fully estimated, but the intriguing case here reported suggests that it may be greater than previously assumed. The demonstration of a modification of the cerebrovenous function with both clinical manifestation and via TMS suggests that the hampered cerebral venous return may contribute to the clinical course of MS.

[Clinical case: post-traumatic thoracic aorta rupture. Considerations on emergency room treatment]. / Rottura post-traumatica dell'aorta toracica. Considerazioni sul trattamento sala di emergenza.

A clinical case of post-traumatic rupture of the thoracic aorta at isthmus and descending aorta levels with favourable outcome is reported. Early suspicion of a possible aortic lesion related to the trauma modality which was characterized by sudden deceleration, immediate performance of a CT scan of the thorax with and without contrast medium and careful monitoring of arterial pressure which showed hypotension at controls during the stay in the emergency and radiological rooms, permitted us to opt for conservative treatment of the lesion with satisfactory outcome.

Sodium cromoglycate in the treatment of eosinophilic gastroenteritis.

Two patients suffering from eosinophilic gastroenteritis (EG) were treated with sodium cromoglycate (SCG). Before treatment they showed enteric and cutaneous symptoms, such as abdominal pain, nausea, vomiting, diarrhoea and recurrent urticaria and angioedema. The histological findings were a notable amount of eosinophilic infiltration in the lamina propria and gastric glands, a villous shortening and thickening and weak eosinophilic inflammation in the duodenum. The patients were treated with 300 mg SCG, 4 times daily, for 4/5 months. During treatment, the clinical symptoms disappeared and at the end of treatment a reduced inflammation with an almost complete decrease of eosinophilic infiltration was observed. The results provide evidence of SCG efficacy in the treatment of EG and suggest its employment as an alternative to the steroids commonly used in EG.