Effectiveness of calretinin and role of age in the diagnosis of Hirschsprung disease.

OBJECTIVE: Gold standard in Hirschsprung disease (HD) diagnosis is rectal suction biopsy (RSB) with hematoxylin and eosin and acetylcholinesterase (ACE) stainings. Sensitivity is 83-93 % and specificity is between 95 and 99 %. The rate of non-conclusive results (NC) due to inadequate samples or variability in the interpretation is about 11-37.8 %. Interpretation is still difficult in neonates. Calretinin (C) is a calcium-binding protein, expressed in the nervous system. It has been introduced as a marker to improve the diagnosis accuracy in HD. We compare sensitivity, specificity between ACE and ACE + C and investigate whether the introduction of C could reduce the rate of inconclusive results. We also tried to define the most adequate age to obtain accurate results from RSB. METHODS: Data from patients undergoing rectal suction biopsies from 2005 to 2014 was analyzed. Until 2010 we used ACE; since 2011 we used ACE + C. The ROC curve analysis of the NC results regarding the age, showed an optimal cut-off point at 1.5 months (m). It divides the sample into two groups which we compared. RESULTS: We analyzed 91 patients. Results of the RSB: 40 HD (44 %), 34 no Hirschsprung (37.4 %) and 17 NC (18.7 %). Sensitivity = 97.5 %, specificity = 97.1 %, not including the NC (1 false positive, 1 false negative). Results depending on the staining: ACE (n = 58) (%) ACE + C (n = 33) (%) p Sensitivity 96 100 1 Specificity 94.7 100 1 NC 24.1 9.1 0.077 Results depending on the age: <1.5 m (n = 27) (%) >1.5 m (n = 64) (%) p Sensitivity 92.3 100 0.325 Specificity 100 96.8 1 NC 40.7 9.4 0.001 CONCLUSION: Calretinin decreases the rate of inconclusive results, but not significantly. The percentage of inconclusive results decreases in patients olders than 1.5 m. Further studies are necessary to determine if this technique is useful to improve RSB results in infants younger than 1.5 months.

Enfermedad de Alzheimer de inicio precoz con esclerosis lateral amiotrófica concomitante / No disponible

Fundamento y objetivo: Descripción clínica, neuropatológica y genética de un paciente con una enfermedad de Alzheimer (EA) de inicio precoz asociada a enfermedad de motoneurona. Paciente: Varón de 58 años de edad con trastorno progresivo de conducta, alteraciones de lenguaje y deterioro cognitivo y funcional de 10 años de evolución que en su estadio final presentó un cuadro de enfermedad de motoneurona con amiotrofia y fasciculaciones en extremidades y cinturas, con rápida evolución a tetraparesia, disfagia severa y disminución progresiva de consciencia. Resultados: En el estudio neuropatológico post mortem se observó una marcada patología de tipo Alzheimer con alta densidad de placas seniles, ovillos neurofibrilares (estadio VI de Braak) y moderada angiopatía amiloide, así como afectación de motoneurona superior e inferior del tipo esclerosis lateral amiotrófica (ELA) con inclusiones del tipo «skeinlike » positivas para ubicuitina/TDP-43 en neuronas motoras. Conclusiones: De esta última se conoce su asociación con la demencia frontotemporal, pero, en cambio, hay muy pocos casos descritos de ELA en presencia de EA de inicio precoz. Es necesaria la aportación de nuevos estudios, ya que existen pocos datos todavía que permitan afirmar con certeza si existe un mecanismo patogénico común o se trata de dos patologías independientes(AU)

Background and aims: To describe clinical, neuropathological and genetic aspects of a patient who developed earlyonset Alzheimer disease and associated motor neuron disease. Patient: A 58 year old man presented progressive behavioural and language alteration with cognitive and functional decline, which slowly progressed during 10 years. In the last disease stages clinical features of upper and lower motor neuron disease appeared with muscular atrophy and fasciculations which rapidly evolved towards tetraparesia, severe dysphagia, and progressive diminution of consciousness. Results: Post-mortem neuropathological examination showed advanced Alzheimertype pathology with frequent neuritic plaques, extensive neurofibrillary pathology (Braak’s stage VI) and moderate amyloid angiopathy with concomitant involvement of upper and lower motor neurons with features of amyotrophic lateral sclerosis with intraneuronal, «skein-like» ubiquitin / TDP-43 protein inclusions. Conclusion: The association of ALS and FTLD is already known. In contrast, ALS in advanced, early-onset Alzheimer disease is rare. More studies are needed to clarify whether there is a common pathogenic process underlying both diseases, or whether they should be considered two independent pathologies(AU)