Predictors of Mechanical Ventilation in Guillain-Barré Syndrome with Axonal Subtypes.

BACKGROUND: The early clinical predictors of respiratory failure in Latin Americans with Guillain-Barré syndrome (GBS) have scarcely been studied. This is of particular importance since Latin America has a high frequency of axonal GBS variants that may imply a worse prognosis. METHODS: We studied 86 Mexican patients with GBS admitted to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a referral center of Mexico City, to describe predictors of invasive mechanical ventilation (IMV). RESULTS: The median age was 40 years (interquartile range: 26-53.5), with 60.5% men (male-to-female ratio: 1.53). Most patients (65%) had an infectious antecedent (40.6% gastrointestinal). At admission, 38% of patients had a Medical Research Council (MRC) sum score <30. Axonal subtypes predominated (60.5%), with acute motor axonal neuropathy being the most prevalent (34.9%), followed by acute inflammatory demyelinating polyneuropathy (32.6%), acute motor sensory axonal neuropathy (AMSAN) (25.6%), and Fisher syndrome (7%). Notably, 15.1% had onset in upper limbs, 75.6% dysautonomia, and 73.3% pain. In all, 86% received either IVIg (9.3%) or plasma exchange (74.4%). IMV was required in 39.5% patients (72.7% in AMSAN). A multivariate model without including published prognostic scores yielded the time since onset to admission <15 days, axonal variants, MRC sum score <30, and bulbar weakness as independent predictors of IMV. The model including grading scales yielded lower limbs onset, Erasmus GBS respiratory insufficiency score (EGRIS) >4, and dysautonomia as predictors. CONCLUSION: These results suggest that EGRIS is a good prognosticator of IMV in GBS patients with a predominance of axonal electrophysiological subtypes, but other early clinical data should also be considered.

Cardiovascular dysautonomia in Achalasia Patients: Blood pressure and heart rate variability alterations.

Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS.

Coexistence of Fragile-X Syndrome, 8p23.1 Deletion, and Balanced Translocation t(7;10)(p10;q24) in a Single Family.

Aims: Fragile-X syndrome (FXS) is the most common inherited form of intellectual disability; it is caused by an abnormal CGG-repeat expansion at the FMR1 gene. However, a few cases of girls with mutations in the FMR1 gene have been reported in the literature. In this study, we describe the clinical and genetic assessment of a family who exhibits the unusual coexistence of FXS, an 8p23.1 deletion, and balanced translocation t(7;10)(p10;q24) in multiple members, including a symptomatic girl with FXS. Materials and Methods: All of the family members underwent comprehensive clinical and neurological examinations. All members of the family were also molecularly diagnosed using a combination of fluorescent-polymerase chain reaction (PCR), Triplet Repeat Primed-PCR, capillary electrophoresis, and karyotyping. Results: We identified a male proband and a female patient that presented with the craniofacial characteristics of FXS, neuropsychomotor developmental delay, speech delay, intellectual deficit, and a positive molecular diagnosis of FXS. Interestingly, the female patient presented with a severe phenotype also associated with the presence of 8p23.1 deletion, while the proband patient presented a balanced translocation t(7;10)(p10;q24). Moreover, we detected multiple carriers of the FXS premutation in the family. Conclusions: To our knowledge, we describe for the first time the simultaneous occurrence of FXS and an 8p23.1 deletion and their possible synergistic effects on the phenotype of a female patient. Moreover, we describe the coexistence of FXS, an 8p23.1 deletion, and a balanced translocation t(7;10)(p10;q24) in the same family.

Bilateral Proximal Forearm Transplantation: Case Report at 7 Years.

BACKGROUND: Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT. CASE PRESENTATION: A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force. RESULTS: Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year. CONCLUSIONS: Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.

Pharmacological Stimulation of Neuronal Plasticity in Acquired Brain Injury.

INTRODUCTION: Brain injuries are one of the leading causes of disability worldwide. It is estimated that nearly half of patients who develop severe sequelae will continue with a chronic severe disability despite having received an appropriate rehabilitation program. For more than 3 decades, there has been a worldwide effort to investigate the possibility of pharmacologically stimulating the neuroplasticity process for enhancing the recovery of these patients. OBJECTIVE: The objective of this article is to make a critical and updated review of the available evidence that supports the positive effect of different drugs on the recovery from brain injury. METHOD: To date, there have been several clinical trials that tested different drugs that act on different neurotransmitter systems: catecholaminergic, cholinergic, serotonergic, and glutamatergic. There is both basic and clinical evidence that may support some positive effect of these drugs on motor, cognitive, and language skills; however, only few of the available studies are of sufficient methodological quality (placebo controlled, randomized, blinded, multicenter, etc) to make solid conclusions about their beneficial effects. CONCLUSIONS: Currently, the pharmacological stimulation of neuroplasticity still does not have enough scientific evidence to make a systematic therapeutic recommendation for all patients, but it certainly is a feasible and very promising field for future research.

Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus-host disease after allogeneic stem cell transplantation.

Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Long-term results of placental blood allografting using reduced-intensity conditioning: multicenter experience in a developing country.

BACKGROUND: Placental blood (PLB) hematopoietic stem cell transplantation has recently been explored in an increasing number of patients; the best conditioning regimen has not been established. MATERIAL AND METHODS: In an eight-year period, 66 consecutive patients, both children and adults (40 males and 26 females), were grafted with allogeneic placental blood cells using a reduced-intensity conditioning regimen: 23 patients were grafted because of a non-malignant condition and 43 patients for a malignant disease. The median age was 7 years (range 5 months to 72 years). RESULTS: Median time to recover >0.5×10(9)/l granulocytes was 19 days, whereas median time to recover >20×10(9)/l platelets was 23 days. Thirty-eight individuals failed to engraft and they either recovered endogenous hematopoiesis or died. Patients have been followed for periods ranging from 0.5 to 66 months, median 9 months. The median overall post-transplant survival (OS) was 22 months and the 36-month OS was 32%; it was significantly better for individuals grafted with 6/6 matched cords (45%). The cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and grade III-IV acute GVHD for the patients who engrafted were 33 and 10%, respectively. DISCUSSION: The low engraftment rate should be improved by selecting better cord blood units; additional studies are needed to define if non-myeloablative conditioning is preferable over conventional conditioning.

Core binding factor acute myeloid leukemia (CBF-AML) in México: a single institution experience.

Twenty one patients with CBF-AML presented prospectively in the Centro de Hematología y Medicina Interna de Puebla (Puebla, México) between February 1995 and March 2010, 14 with the t(8;21)(q22;q22) and 7 with the inv(16)(p13;q22)/t(16;16)(p13;q22); they represent 13% of all cases of AML. The median age of the patients was 24 years (range 1 to 61). Seven of 14 patients with t(8;21)(q22;q22) had an M2 morphology whereas 3/7 with the inv(16) had an M4 morphology; in addition to the myeloid markers identified by flow-cytometry (surface CD13, surface CD33, and cytoplasmic myeloperoxidase) lymphoid markers were identified in the blast cells of 8/14 cases of the t(8;21) patients, but in no patient with the inv(16). Nineteen patients were treated with combined chemotherapy and 16 (84%) achieved a complete molecular remission. Seven patients were auto or allografted. Relapses presented in 10/16 patients. The median probability of overall survival (OS) has not been reached being above 165 months, whereas the 165-month probability of OS and leukemia-free survival was 52%; despite a tendency for a better outcome of patients with the t(8;21), there were no significant differences in survival of patients with either the t(8;21) or the inv(16). In this single institution experience in México, we found that the CBF variants of AML have a similar prevalence as compared with Caucasian populations, that the co-expression of lymphoid markers in the blast cells was frequent in the t(8;21) and that these two AML subtypes were associated with a relatively good long-term prognosis. Further studies are needed to describe with more detail the precise biological features of these molecular subtypes of acute leukemia.