Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Serum vitamin D deficiency in subjects with severe acquired brain injury and relationship with functional severity.

BACKGROUND: Vitamin D may be important for the development and function of the nervous system. Low serum vitamin D levels have been detected in several neurological diseases. OBJECTIVE: To ascertain the relationship between 25(OH)D serum level and disability in subjects with severe acquired brain injury (sABI). DESIGN: Prospective cross-sectional study Methods: Consecutive subjects with sABI admitted to neuro-rehabilitation were enrolled. A sample of subjects from the neurological ward was considered the control group. Vitamin D serum levels and blood parameters were measured at admission. Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS), and Level of Cognitive Functioning (LCF) were used in assessing disability. RESULTS: A total of 104 subjects (34 F, 70 M; mean age 53.9 ± 15.2 years) were enrolled: 54 (19 F, 35 M) with sABI and 50 (15 F, 35 M) subjects as control group. Deficient mean serum levels of vitamin D (19.2 ± 9.4 ng/mL) were detected in the subjects with sABI and a significant inverse correlation between vitamin D serum levels and DRS score was detected (p = 0.04). CONCLUSION: Subjects with sABI showed vitamin D deficiency that might correlate to disability severity. The reason is unclear and might represent a secondary phenomenon resulting from the inflammatory process.

Long-term functional outcome and health status of patients with critical illness polyneuromyopathy.

OBJECTIVE: The aim of this study was to investigate the long-term functional outcome and health status of patients with critical illness polyneuromyopathy (CIPNM). METHOD AND SUBJECTS: One hundred and twenty-four consecutive survival intensive care unit patients admitted to a neuro-rehabilitation Unit from January 2003 to December 2007 were identified. Patients with proven CIPNM by the electromyography were prospectively followed. The Barthel and modified Rankin Scales (mRS) were administered to all patients at baseline, discharge and follow-up. The SF-36 questionnaire was administered to ascertain health status. Each patient underwent an individually tailored rehabilitation therapy. RESULTS: Forty-two subjects (23M, 19F, mean age 58.4 ± 13.9) were enrolled. Of these, 30 patients were diagnosed electrophysiologically with CIP, six with critical illness myopathy (CIM) and six with a finding combination of CIP and CIM (CIP/CIM) subtype. The mean Barthel scores at baseline, discharge and follow-up were 16.7 ± 8.6, 81.7 ± 16.4 and 86.7 ± 15.9 (P < 0.001) and the median mRS scores were 5 (IQR: 5-5), 3 (IQR: 0-5) and 1 (IQR: 0-5). The mean length of neuro-rehabilitation stay was 76.2 ± 28.1 days. The SF-36 questionnaire administered at follow-up (mean 31.7 ± 15.8 months), showed significantly lower values compared to Italian normative. CONCLUSION: ICU patients with CIPNM treated in a neuro-rehabilitation setting resulted in a good functional outcome. Despite complete recovery, patients with CIPNM experienced difficulties in health status.

Prolonged remission of neuro-Behcet disease following autologous transplantation.

Two young male patients with severe progressive Behcet's disease with neurological involvement (N-BD) were treated by high-dose immunosuppressive chemotherapy (HIC) followed by autologous CD34+ selected peripheral blood stem cell transplantation (APBSCT). Neurological impairment and disability were quantified by means of Expanded Disability Status Scale (EDSS). Neuroimaging included spine and brain MRI and brain SPECT by radiolabeling technetium (Tc99m) Ethyl Cisteynate Dimer (ECD). Disease progression halted after treatment in both patients. At 48 months of follow-up they were therapy-free and one showed neurological status and disability improvement. Brain MRI findings were unchanged in both patients, but SPECT-ECD showed an increase of blood flow in the hypoperfused cerebral areas in the ameliorated patient. Immune ablation followed by APBSCT can modify the course of severe N-BD. Because of the high risk and the transplant-related mortality, these cases have to be carefully selected.

Brain MRI white matter lesions in migraine patients: is there a relationship with antiphospholipid antibodies and coagulation parameters?

Brain magnetic resonance imaging (MRI) studies in migraine patients have demonstrated lesions consisting of focal regions of increased signal intensity within the white matter. Antiphospholipid antibodies are known to have a role in many diseases including migraine. The aim of the present study was to ascertain the relationship between MRI-visualized cerebral focal hyperintense lesions and serum antiphospholipid antibody levels, as well as blood coagulation parameters in migraine patients. One hundred and two (77 females, 25 males, mean age 33.8 +/- 11.1) consecutive migraine patients and a control group of 94 (70 females, 24 males, mean age 33.2 +/- 10.8) healthy subjects were enrolled. All individuals underwent brain MRI. Complete blood examinations, autoantibodies, antiphospholipids antibodies including anticardiolipin and lupus anticoagulant (aCL, LAC), antithrombin III, Protein C and S serum levels were ascertained in the subjects who presented white matter lesions on MRI. Twenty-seven (26.4%) migraine patients and six (6.3%) healthy subjects in the control group showed focal regions of increased intensity signal within cerebral white matter (odds ratio 5.3, 95% CI: 1.98-16.36). In migraine patients with white matter lesions, antiphospholipid antibodies were not detected and serum levels of antithrombin III, and proteins C and S were normal. White matter lesions in migraine patients are fairly common. This finding is not associated with antiphospholipid antibodies or abnormal coagulation parameters. The significance of such lesions at present remains unclear.

Botulinum toxin type-A and plaster cast treatment in children with upper brachial plexus palsy.

BACKGROUND AND PURPOSE: Electrical stimulation, physical therapy and occupational therapy remain the main treatment for children with upper brachial plexus palsy (UBPP), when surgery has been excluded. A pilot study was undertaken to investigate whether botulinum toxin type A (BoNT-A) and plaster casting, as adjunct to the physical therapy, decreased muscle contracture and improved the position and function of the impaired arm. METHOD: Twenty-two children (mean age 5.6 +/- 3.4 years) with mild UBPP who previously underwent serial cast treatment, unsuccessfully, were enrolled. Neurological impairment and functional status were quantified using Medical Research Council (MRC) and Mallet scales and the Nine-Hole Peg Test (NHPT). Elbow extension was measured using a goniometer. Biceps brachii, brachialis, pronator teres and pectoralis major muscles were injected with 22 units kg(-1) BoNT-A (Dysport, Ipsen). After injection, the treated arm was fixed with a plaster cast and progressively lengthened over 14 days. The cast was maintained for 30 days. Assessments of elbow extension, MRC, Mallet Scale and NHPT were made at baseline, 3, 6 and 12 months. RESULTS: After BoNT-A injection, children had significant improvement of active elbow extension (15.5 degrees +/- 17.1 at 12 months after injection, compared with 42.0 degrees +/- 10.4 at baseline; p < 0.001). NPHT scores improved significantly over the 12 months (51.1 +/- 21.8 seconds compared with 56.7 +/- 19.3 seconds at baseline, p < 0.01). MRC and Mallet scale scores of the paretic muscles were unchanged. CONCLUSION: The children showed a reduction in muscular contracture and improvements of the arm position and elbow extension. The data support the use of BoNT-A and plaster casting as an adjunct to physical therapy, in the treatment of children with mild UBPP.

Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients.

Experimental evidence indicates that tumor necrosis factor alpha (TNF-alpha) is involved in brain damage following ischemic injury. The present study was designed to monitor serum TNF-alpha levels in acute stroke patients and to correlate TNF-alpha levels with lesion size, neurological impairment and vascular risk factors. In 41 patients with ischemic stroke, serum TNF-alpha levels were serially measured by a solid enzyme amplified sensitivity immunoassay (EASIA) in the first 10 days after stroke onset. Serum fibrinogen and C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts were determined on the same days to monitor acute phase response changes. Lesion size was calculated on computed tomograms by a computer-assisted procedure. Neurological impairment was evaluated on the Canadian Neurological Scale. Forty age-matched subjects were used as controls. Compared to baseline, TNF-alpha levels significantly increased during the study ( p=0.0001), peaking on day 7. Peak TNF-alpha levels did not correlate with neurological impairment or lesion size. Multivariate analysis showed that sex, age, vascular risk factors and infectious complications did not influence TNF-alpha levels. Fibrinogen, CRP, WBC and neutrophil concentrations increased, indicating an acute phase response occurred after stroke. In conclusion, serum TNF-alpha levels showed an early and prolonged increase after stroke onset, unrelated to lesion size, neurological impairment, age, sex, vascular risk factors or infectious complications. Serum increase of TNF-alpha may be explained as part of the acute phase response occurring in stroke patients.

Incidence of first-ever ischemic and hemorrhagic stroke in a well-defined community of southern Italy, 1993-1995.

Most epidemiological surveys in the Italian population, have concentrated on areas of northern and central Italy. The incidence of the first-ever ischemic and hemorrhagic strokes in a well-defined population of the province of Foggia, a rural area of southern Italy, over a 3-year period has been investigated, to compare the occurrence of stroke by type in this and other areas. A retrospective study in a local health district (USL FG3) in the province of Foggia was conducted and all cases of first-ever cerebral infarction (CI) and intracerebral hemorrhage (ICH) in the local population (41 269) from January 1, 1993 to December 31, 1995 have been investigated. Case ascertainment was performed by a chart review in the two local hospitals and examination of death certificates. General practitioners were also asked to report on non-hospitalized cases suffering a stroke during the study period. Patients with recurrent stroke, unclassifiable stroke, transient ischemic attacks and subarachnoid hemorrhage were excluded. Risk factors for stroke and 30-day mortality were investigated. The rates were standardized to the Italian population (57 138 489, 1991 census). During the 3-year study period, 202 patients had a first-ever ischemic or hemorrhagic stroke (66 in 1993, 69 in 1994 and 67 in 1995). Of these, 174 (86.1%) had cerebral ischemia, accounting for 57, 60 and 57 cases in the three index years. The overall crude annual incidence of CI and ICH was 1.60, 1.67 and 1.62 of 1000 for 1993, 1994 and 1995, respectively. The corresponding standardized incidences rates were 2.0, 2.10 and 2.06 of 1000. The rate was 0.11 in patients <55 years of age, and 1.97, 7.01, 13.52, and 25.34 at ages 55-64, 65-74, 75-84, and 85+ years for the entire period; the 30-day mortality was 27.2, 21.7, and 15% for 1993, 1994, and 1995, respectively. Hypertension (45.9%), diabetes (26.4%) and atrial fibrillation (16.6%) were the most common risk factors. The incidence of CI and ICH was similar to that of most other Italian studies. It was constant during the 3-year period, and mostly involved older people.

Occurrence of factor V Leiden mutation (Arg506Gln) and anticardiolipin antibodies in migraine patients.

The occurrences of factor V Leiden mutation (Arg506Gln) and antiphospholipid antibodies (APA) in migraine patients have been reported, but the findings are controversial. We investigated the presence of factor V Leiden and the serum level of anticardiolipin antibodies (aCL) in a consecutive series of 70 migraine patients (47 women; mean age, 34.1 years). Of these, 40 patients had migraine with aura. A matched sample of 70 healthy people was considered as the control group. Heterozygous genotype for factor V Leiden mutation was detected in 4 (5.7%) migraine patients (of which 2 had migraine with aura) and in 2 (2.8%) subjects of the control group. Although proportionally more migraine patients harbored the factor V Leiden mutation, this difference was not statistically significant, perhaps due to the small number of patients involved. We found normal serum levels of aCL in all migraine patients. Further studies and a long-term follow-up are warranted to determine the significance of this genetic abnormality in migraine.

Bilateral periventricular nodular heterotopia associated with coeliac disease and palatoschisis.

Periventricular nodular heterotopia (PNH) is considered a distinct entity in relation to the other forms of neuronal migration disorders (NMD), because PNH patients usually have normal neurological and mental examination results. We report the case of a 48-year-old woman with bilateral periventricular nodular heterotopia associated with epilepsy, coeliac disease, palatoschisis and other dysmorphic features. Her intelligence quotient (I.Q.) and the results of a neurological examination were normal, but she suffered from a drug-resistant epileptic syndrome characterised by predominantly generalised and sporadic partial seizures. It has recently been suggested that an X-linked dominant inheritance may play a role in bilateral periventricular nodular heterotopia, and it is thought that a genetic defect is probably responsible for coeliac disease. In our patient, a genetic disorder may have produced both diseases and the dysmorphic syndrome, although the coexistence of PNH, epileptic seizures, coeliac disease and palatoschisis could be coincidental. Further observations are needed to ascertain whether the simultaneous presence of these disorders is simply an unusual association of unrelated pathologies or a new and distinct pathological entity.

[The use of type A botulin toxin in the treatment of detrusor-sphincter dyssynergia]. / L'impiego della tossina botulinica tipo A nel trattamento della dissinergia detrusore sfintere.

The detrusor-sphincter dyssynergia (DSD) is a common and significant problem for patients with spinal cord lesions. If not treated, DSD can lead to severe and potentially lethal complications (urinary tract infections and renal damage). BTX inhibits acetylcholine release at the neuromuscular junction, producing muscle chemical denervation in the site of injection. The aim of this preliminary study was to test the safety and the effects of BTX injection in the spastic urethral rhabdosphincter in patients with DSD. Five patients (3 M, 2 F; mean age 43 years, range 22-56) with DSD entered the study. Videourodynamic parameters were controlled before BTX injection at 10 days, at 3 and 6 months after infiltration. The aim of this preliminary study was to test the safety and the effects of BTX injection in the spastic urethral rhabdosphincter in patients with DSD. The post void residual urine volume, the maximum pressure of emptying and the maximum pressure of urethral closure are reported in Tab. II-III-IV. Patients reported subjective improvement of bladder emptying and improved quality of life. No adverse effects related to pharmacological activity of BTX or to infiltration procedures were observed.

Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke.

BACKGROUND AND PURPOSE: Alterations of gait cycle and foot-drop on the paretic limb are characteristic of stroke patients. Electromyographic biofeedback treatment has been used in rehabilitation of walking, but results are controversial. We performed gait analysis to evaluate the efficacy of electromyographic biofeedback compared with physical therapy. METHODS: Sixteen patients with ischemic stroke were enrolled in the study. The experimental group (4 men, 4 women) received electromyographic biofeedback treatment together with physical therapy. The control group (5 men, 3 women) was treated with physical therapy only. Clinical and functional evaluations before and after treatment were performed using Canadian Neurological, Adams, Ashworth, Basmajian, and Barthel Index scales. Computerized gait analysis was performed in all patients. RESULTS: Electromyographic biofeedback patients showed significantly increased scores on the Adams scale (P < .05) and Basmajian scale (P < .01). Gait analysis in this group showed a recovery of foot-drop in the swing phase (P < .02) after training. CONCLUSIONS: Our data confirm that the electromyographic biofeedback technique increases muscle strength and improves recovery of functional locomotion in patients with hemiparesis and foot-drop after cerebral ischemia.

Mesial temporal cortex hypoperfusion is associated with depression in subcortical stroke.

BACKGROUND AND PURPOSE: This study was conducted to evaluate local cerebral blood flow changes in patients with depression after a subcortical stroke. METHODS: Clinical and neuropsychological assessments were performed in 15 patients with a single subcortical lesion. Depression was assessed by DSM-III-R. In addition, the Hamilton Rating Scale for depression, the Zung Self-Rating Depression Scale, and the Beck scale were administered to each patient. Single-photon emission-computed tomography study was performed with 99mTc hexamethylpropyleneamine oxime. RESULTS: In all patients cortical regions ipsilateral to subcortical lesions were significantly less perfused than the contralateral cortex. Cerebral blood flow values were significantly lower in depressed patients (n = 8) than in nondepressed patients (n = 7) only in the mesial temporal cortex of the affected hemisphere. Cerebral blood flow values in the mesial temporal cortex of the affected hemisphere significantly correlated with the severity of depression. CONCLUSIONS: Temporal lobe hypoperfusion may reflect a dysfunction of the limbic system, suggesting that this location may be critical for the occurrence of depressive symptoms in patients with subcortical stroke.

Leukocyte response in patients suffering from acute stroke.

The oxidation of adrenaline to adrenochrome has been shown to reflect the activation of leukocytes in vivo. We tested the in vivo activation of leukocytes by measuring plasma oxidation of adrenaline to adrenochrome in patients suffering from cerebral ischemia, cerebral hemorrhage, and transient ischemic attacks and in healthy subjects. Patients with cerebral ischemia and cerebral hemorrhage had significantly higher values than healthy subjects, while patients with transient ischemic attacks had values similar to those of healthy subjects. In some patients with cerebral ischemia, the test was repeated 4 and 15 days after the acute event, but the follow-up data did not differ from baseline values. Our study shows that leukocyte activation occurs in cerebral ischemia and cerebral hemorrhage.