ArticlePDF Available

Sustained clinical remission in a patient with remittent-recurrent multiple sclerosis and celiac disease gluten-free diet for 6 years

Authors:
Article

Sustained clinical remission in a patient with remittent-recurrent multiple sclerosis and celiac disease gluten-free diet for 6 years

lesión cerebelosa no se asocia con signos cerebelosos. Es posible que
la mayoría de las lesiones interrumpan la vía corticopontocerebelosa
de manera amplia y no selectiva, como ocurre en la ataxia-hemipa-
resia, que es necesaria para que se produzca una ataxia manifiesta.
Recientemente, Nelissen et al.12 describieron DCC en 11 pacientes
con epilepsia refractaria secundaria a esclerosis mesial temporal que
quedaron libres de crisis tras cirugía. Para ello realizaron en todos ellos
un FDG-PET interictal y un SPECT de perfusión, tanto ictal como inte-
rictal, y observaron que el hipometabolismo interictal en PET y la hipo-
perfusión ictal en SPECT fue mayor en el lóbulo frontal ipsilateral. La
hipoperfusión del lóbulo frontal ictal se asoció con DCC. El lóbulo
temporal ipsilateral mostró una hiperperfusión ictal máxima y un
hipometabolismo interictal intermedio, si se compara con el grado de
hipometabolismo que afectó a los lóbulos frontales. Se especula que
la fisiopatología de la DCC se relaciona con la persistencia del fenó-
meno irritativo epiléptico que reduciría el metabolismo y flujo sanguí-
neo en el hemisferio cerebeloso contralateral al inhibir su metabolismo
interrumpiendo la vía glutamatérgica corticopontocerebelosa.
Esta paciente ilustra el efecto estructural nocivo de un fenómeno
epiléptico sostenido en el lóbulo frontal y, aunque no puede asegurar-
se, probablemente, el desarrollo posterior de una esclerosis mesial. Esto
nos induce a pensar que la actuación precoz sobre la epilepsia con tera-
pias agresivas, cuando aún el daño de la vía córticopontocerebelosa es
solamente metabólico, potencialmente podríamos ser capaces de evi-
tar la hemiatrofia corporal secundaria a la lesión cerebral establecida.
BIBLIOGRAFÍA
1. Recio MV, Gallagher MJ, Malean MJ, Abou Khalil B. Clinical features of
epilepsy in patients with cerebellar structural abnormalities in a referral
center. Epilepsy Res 2007;76:1-5.
2. Velasco F, Velasco AL, Velasco M, Carrillo-Ruiz JD, Castro G, Núñez JM.
Central nervous system neuromodulation for the treatment of epilepsy.
Neurochirurgie 2008;54:418-27.
3. Shik WJ, Huang WS, Milan PP. F-18 FDG PET demonstrates crossed cere-
bellar diaschisis 20 years after stroke. Clin Nucl Med 2006;31:259-61.
4. Shetty-Alva N, Novotny EJ, Shetty T, Kuo PH. Positron emisin tomography
in Rasmussen’s encephalitis. Pediatr Neurol 2007;36:114.
5. Patronas NJ, DiChiro G, Smith BH, De La Paz R, Brooks RA, Milan HL, et al.
Depressed cerebral glucose metabolism in supratentorial tumours. Brain
Res 1984;291:93-101.
6. Mewasingh LD, Christiaens F, Aeby A, Christophe C, Dan B. Crossed cere-
bellar diaschisis secondary to refractory frontal seizures in frontal child-
hood. Seizure 2002;11:489-93.
7. Sechi G, Casu AR, Rosati G, Spanu A, Deserra F, Nuvoli, et al. Cerebral and
cerebellar diaschisis following carbamazepine therapy. Prog Neuropsycho-
pharmacol Biol. Psychiatry 1995;19:889-901.
8. Ogasawara K, Kobayashi M, Komorbayashi M, Fukida T, Inoue T, Tirasaki K, et
al. Transient crossed cerebellar diaschisis secondary to cerebral hyperperfu-
sion following carotid endarterectomy. Ann Nuc Med 2005;19:321-4.
9. Kastenbauer S, Schulz Schaefer WJ, Tatsch K, Yousry TA, Kretzshmar HA,
Pfister HW. Crossed cerebellar diaschisis: a clue to the mechanism of ata-
xia hemiparesis in Creutzfeld Jakob disease. J Neurol 2001;248:1993-4.
10. Dudick DW, Roarke MC. Crossed cerebelar diaschisis during migraine with
prolonged aura: a possible mechanism for cerebellar infarctions. Cepha-
lalgia 2007;28:83-6.
11. Sobesky J, Thiel A, Ghaemi M, Hilker RH, Rudolf J, Jacobs AH, et al. Cros-
sed cerebellar diaschisis in acute human stroke: a PET study of serial chan-
ges and response to supratentorial reperfusion. J of cerebral blood flow &
metab. 2005:25;1685-91.
12. Nelissen N, Van Paesschen W, Baete K, Van Laere K, Palmini A, Van Billoen
H, et al. Correlation of interictal FDG-PET metabolism and ictal SPECT per-
fusion changes in human temporal lobe epilepsy with hipocampal sclero-
sis. Neuroimage 2006;32:684-95.
Remisión clínica sostenida en paciente
con esclerosis múltiple tipo remitente-
recurrente y enfermedad celíaca
con dieta sin gluten durante 6 años
La esclerosis múltiple (EM) es una enfermedad inflamatoria de
naturaleza autoinmune relacionada con factores genéticos y am-
bientales no conocidos, cuya forma de inicio más frecuente es la re-
mitente-recurrente (RR)1. La enfermedad celíaca (EC) es otro proceso
autoinmune con factores genéticos de susceptibilidad conocidos y
relacionada con un factor exógeno, el gluten, conjunto de proteínas
incluidas en la harina del trigo y otros cereales.
La EC era considerada hasta hace poco un proceso infrecuente y de
aparición infantil. Se reconoce, en cambio, ahora como muy prevalente
yquepuedemanifestarseacualquieredaddelavida.Cursaconinfla-
mación de la mucosa del intestino delgado, pero también puede ocasio-
nar múltiples trastornos en diversos órganos2.Haypocoscasosdescritos
de asociación entre EM y EC y se han seguido durante corto tiempo3,4.
Cartas al director
Neurología 2009;24(3):209-216 21391
Figura 2 A) Resonancia magnética (RM) axial en T2 que
muestra atrofia del hemisferio cerebral derecho evidenciada por
la dilatación de los surcos y el aumento del calibre ventricular con
hiperintensidad en el hipocampo derecho compatible con esclero-
sis mesial. B) RM en FLAIR con severa atrofia global del hemisfe-
rio derecho y dilatación del sistema ventricular asociado a incre-
mento de la profundidad de los surcos cerebelosos. C) SPECT cere-
bral con HMPAO muestra hipoperfusión del hemisferio cerebral
derecho y del cerebeloso izquierdo en azul. D) RM sagital muestra
además hipotrofia del cuerpo calloso.
R. Ribacoba1
M. Menéndez1
J. Salas-Puig2
1Unidad de Neurología
Hospital Álvarez Buylla
Mieres
2Servicio de Neurología
Hospital Universitario Central de Asturias
Oviedo
Correspondencia:
Renée Ribacoba Montero
Unidad de Neurología
Hospital Álvarez Buylla
Murias, s/n
33616 Mieres (Asturias)
Correo electrónico: rribacoba@gmail.com
Recibido el 12-9-08
Aceptado el 11-11-08
Presentado en la Reunión Anual de la SNA. Oviedo, 2008.
Presentamos el caso clínico de una paciente de 29 años en la que se
diagnosticaron sucesivamente las dos enfermedades con una evolución muy
favorable de ambas, siguiendo dieta sin gluten (DSG) desde hace 6 años.
Ahora, hace 9 años, empezó su sintomatología, en forma de hemipares-
tesias en el lado izquierdo, salvo en la cara, que remitieron espontáneamente
en 3 semanas. Al año siguiente ocurrió otro episodio similar, afectando al he-
micuerpo derecho, que también remitió sin secuelas. Un año más tarde, des-
pués del parto de su segundo hijo, tuvo un tercer episodio con dolor cervical
y debilidad en ambas piernas y fue hospitalizada. Los marcadores serológicos
para HIV- 1 y 2, Borrelias, Treponemas y Brucellas fueron negativos, así como
los anticuerpos anticardiolipina. El hemograma yla bioquímica fueron nor-
males, excepto una ligera elevación de ALT= 60 U/L (N<40).
La RM mostró, en la secuencia ponderada de T2, dos lesiones hiperintensas
en C4-C5 yC7-D1, en la médula espinal, yotras nueve en la sustancia blanca ce-
rebral, de predominio periventricular (fig. 1A). Las lesiones eran características de
esclerosis múltiple ycumplían criterios de diseminación espacial. Los potenciales
evocados somatosensoriales (PESS) mostraron una conducción espinal retrasada y
los visuales (PEV) fueron normales. El LCR mostró 15 bandas oligoclonales de IgG,
no presentes en suero. Fue diagnosticada de EMRR clínicamente definida, según
los criterios de Poser5,yrecibió metilprednisolona i.v. ala dosis de 1.000 mg/día
durante 5días, con mejoría clínica significativa. Se comenzó un tratamiento de
mantenimiento con Interferon (IFN) beta 1a 44 mcg s.c. 3veces por semana.
Al cabo de 1 año, la paciente sufrió otro brote, con dolor lumbar, pares-
tesias en piernas y urgencia urinaria, junto a un cuadro abdominal de dolor,
diarrea abundante y pérdida de peso, que precisó de nuevo ingreso hospitala-
rio. Los niveles de anticuerpos antitransglutaminasa (TGt-IgA) estaban muy
elevados, 186 IU/ml (N<10). El tipaje de HLA-II fue positivo, en forma homo-
cigótica, para el gen HLA-DQ2. Las biopsias duodenales pusieron de manifies-
to una atrofia moderada de las vellosidades intestinales (estadío 3b de
Marsh)6. Con el diagnóstico de EC se instauró una dieta sin gluten (DSG) que
ha seguido de forma regular durante 6 años.
Desde el comienzo de la DSG se observó una mejoría notable del estado
general, con recuperación del peso, desaparición de las diarreas ydel dolor
abdominal, no habiendo presentado desde entonces nuevas recidivas de su
EM. La exploración neurológica ha permanecido normal. Los valores séricos
de la TGt-IgA disminuyeron notablemente en los 6 primeros meses y se nor-
malizaron por completo al año. Lo mismo pasó con la ALT. Se repitió la en-
doscopia digestiva alta al cabo de 2 años, con el resultado anatomopatológi-
co de biopsias duodenales normales. Una RM reciente demostró una ligera
disminución del número de lesiones, sin que ninguna captara gadolinio
(fig. 1B). Se suspendió IFN-beta 1a hace 2 años y no ha tenido ninguna otra
medicación desde entonces, continuando asintomática (tabla 1).
Se plantea en esta paciente un problema diagnóstico: saber si
tiene dos enfermedades asociadas o sólo una EC que ha permaneci-
do latente o subclínica mucho tiempo hastaafectar al sistema ner-
vioso central (SNC), con apariencia de brotes y de EMRR, dando des-
pués una exacerbación digestiva característica.
La EC se reconoce ahora comoun proceso muy frecuente, con
unaprevalenciamedia a nivel mundial del 1%. Lasformas atípicas
predominan en el adulto y a veces las manifestaciones iniciales pue-
den presentarse afectando al SNC o periférico7-11.
Pensamos que esta paciente tiene ambas enfermedades. El diag-
nóstico de EMRR, hace 7 años, se basó en tres brotes de mielitis, a di-
ferentes niveles de la médula espinal (diseminación temporal) y una
RM con múltiples lesiones en el SNC (diseminación espacial). Aún su-
frió otro cuarto brote, bajo tratamiento con Interferon beta 1a.
Se handescrito casos de neuromielitis óptica asociados aEC,
con favorable respuesta a la DSG4, pero nuestro caso, en ningún mo-
mento tuvo sintomatología ocular ylos PEV fueron normales. Tam-
bién se ha descrito, en una mujer joven, la asociación de EM con he-
patitis autoinmune y EC subclínica, siguiendo, bajo DSG, una buena
evolución los tres procesos12.
A favor de una base genética común para EM y EC existen algu-
nos datos. En un estudio reciente, realizado en España, sobre una se-
rie de 598 pacientes con EC, frente a 414 con EM y 546 controles sa-
nos, el genotipo para los polimorfismos del receptor de la
Interleuquina 23 (IL 23R) estaba sobreexpresado en ambas enferme-
dades respecto a los controles13. También ambas enfermedades apa-
recen relacionadas con marcadores genéticosdel sistema HLA-I,
como son MIC-AyMIC-B, obserndoseniveles séricos elevados de
la molécula MIC-B, tanto en pacientes de EMRR como de EC, con ac-
tividad inflamatoria14-17.
La respuesta de esta paciente a la DSG ha sido excelente y se ha
mantenido así a lo largo de 6 años. Desaparecieron los síntomas di-
gestivos al poco de ponerla ylamisma evolución favorable siguió
todo lo neurológico. La tasa anualizada de brotes cayó de 1 a 0, en el
primerode DSG yal día de hoy permanece asintomática, con
EDSS=0.
Tras 2 años de DSG, la analítica sanguínea y las biopsias duode-
nales eran completamente normales, y al cabo de 6 años, las lesiones
desmielinizantes habíandisminuido cuantitativamente, sin captar
contraste en una RM de control.
Cartas al director
Neurología 2009;24(3):209-216 92214
Figura 1 A) Resonanciamagnética al diagnóstico.B) Con-
trol al sexto año de dieta sin gluten.Parte superior: A) Imagen axial,
en densidad protónica, de un cortecerebral anivel de los ventrícu-
loslaterales, mostrando una lesión hiperintensa periventricular (fle-
cha). B) Reducción del tamaño de la lesión anterior. Parte inferior:
A) Sección sagital en línea media de la dula espinal cervical, en
secuencia ponderada T2, mostrando una lesión hiperintensa (fle-
cha), en segmentoC7.B) Desaparición de dicha lesión.
A
A
B
B
El IFN-beta 1a no pareció influir en la evolución favorable de la
paciente, ya que sufrió una recaída después de estar poniéndolo du-
rante 1 año, cuando aún no se había instaurado la DSG y, sin embar-
go, a partir de la misma no tuvo nuevos brotes, ni tampoco al sus-
penderlo, hace 2 años.
Hadjivassiliou et al.18 han descrito una serie de pacientes con
sensibilidad al gluten que presentan una enfermedad similar a la EM.
El rasgo clínico predominante es la ataxia. En la RM hay afectación
de la sustancia blanca cerebral y medular, pero las lesiones son dife-
rentes de las que se ven en pacientes con EM. La DSG estabilizó o
mejoró los síntomas neurológicos de sus pacientes, pero las lesiones
de RM no se modificaron.
En nuestro caso, ¿se trata de una EC con lesiones secundarias en
el SNC que se confunden con las de la EM y que responde favorable-
mente, de manera global, a la DSG?, o, más bien, ¿estamos ante el
efecto neuroprotector de la DSG sobre un caso de EMRR, que ade-
más tiene una EC asociada y en remisión bajo DSG?
Se requieren más estudios para evaluar la posible interrelación
entre ambos procesos.
BIBLIOGRAFÍA
1. Compston A, Coles A. Multiple Sclerosis. Lancet 2002;359:1221–31.
2. Green PH, Cellier C. Coeliac disease 2007;357:1731-431.
3. Pengiran Tengah CD, Lock RJ, Unsworth DJ, Wills AJ. Multiple sclerosis
and occult gluten sensitivity. Neurology 2004;62:2326-7.
4. Jacob S, Zarei M, Kenton A, Allroggen H. Gluten sensitivity and neuromye-
litis optica: two cases report. J Neurol Neurosurg Psych 2005;76:1028-30.
5. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al.
New diagnostic criteria for multiple sclerosis: guidelines for research pro-
tocols. Ann Neurol 1983;13:227-31.
6. Marsh MN. Gluten, major histocompatibility complex and the small intes-
tine. A molecular and immunobiological approach to the spectrum of
gluten sensitivity. Gastroenterology 1992;102:330-54.
7. Volta U, De Giorgio R, Petrolini N, Stanghellini V, Bárbara G, Granito A, et al.
Clinical findings and antineuronal antibodies in celiac disease with neu-
rological disorders. Scand J Gastroenterol 2002;37:1276-81.
8. Ludvigsson JF, Olsson T, Ekbom A, Montgomery SM. A population-based
study of celiac disease, neurodegenerative and neuroinflammatory disea-
se. Aliment Pharmaco Ther 2007;25:1317-27.
9. Chin RL, Tseng VG, Green PH, Sander HW, Brannagan TH, Latov N. Multi-
focal axonal polyneuropathy in celiac disease. Neurology 2006;66:1923-5.
10. Hadjivassiliou M, Grünewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA,
Sanders DS, et al. Neuropathy associated with gluten sensitivity. J Neurol
Neurosurg Psychiatry 2006;77:1262-6.
11. Rodrigo L. Celiac disease (Ed). Word J Gastroenterol 2006;12:6585-93.
12. Ferro MT, Franciotta D, Riccardi T, D’Adda E, Mainardi E, Montanelli A.
A case of multiple sclerosis with atypical onset associated with autoim-
mune hepatitis and silent celiac disease. J Neurol Sci 2008;29:29-31.
13. Núñez C, Dema B, Cénit MC, Polanco I, Maluenda C, Arroyo R, et al. IL23R:
a susceptibility locus for celiac disease and multiple sclerosis? Genes Im-
mun 2008;9:289-93.
14. Fernández-Morera JL, Tuñón A, Rodríguez-Rodero S, Rodrigo L, Martínez-
Borra J, González S, et al. Clinical behavior of multiple sclerosis is modulated
by the HMC class I-chain-related gene A. Tissue Antigens 2006;67: 409-14.
15. Fernández-Morera JL, Rodríguez-Rodero S, Lahoz CH, Tuñón A, Astudillo A,
García-Suárez O, et al. Soluble MHC class I chain-related protein B serum
levels correlated with disease activity in relapsing-remitting multiple
sclerosis. Hum Immunol 2008;69:235-40.
16. González S, Rodrigo L, López-Vázquez A, Fuentes D, Agudo-Ibáñez L, Ro-
dríguez-Rodero S, et al. Association of MHC class I related gene B (MICB)
to celiac disease. Am J Gastroenterol 2004;99:676-80.
17. López-Vázquez A, Rodrigo L, Fuentes D, Riestra S, Bousoño C, García Fer-
nández S, et al. MHC class I chain related gene A (MICA) modulates the
development of celiac disease in patients with the high risk heterodimer
DQA1*0501/DQB1*0201. Gut 2002;50:336-40.
18. Hadjivassiliou M, Sanders DS, Grünewald RA. Multiple sclerosis and occult
gluten sensitivity. Neurology 2005;64:933-4.
19. Kurtzke JF. Rating neurologic impairment in Multiple Sclerosis: an Expan-
ded Disability Status Scale (EDSS). Neurology 1983;33:1444-52.
Prurito como manifestación
inicial de un síndrome de la persona
rígida paraneoplásico asociado
a anticuerpos antianfifisina
El síndrome de la persona rígida (SPR) es un trastorno raro del
SNC caracterizado por rigidez muscular progresiva asociado a
espasmos dolorosos. Si bien de forma característica la rigidez afec-
ta de forma predominante a la musculatura axial, se han descrito
casos focales de presentación (síndrome de la pierna o extremidad
rígida), lo que dificulta su diagnóstico1,2. El origen paraneoplásico
es muy infrecuente, en general asociado a anticuerpos antianfifisi-
na (Ac-anfifisina) y cáncer de mama1,2,3-7. Describimos a un varón
en el que el prurito fue la primera manifestación de una forma
focal de SPR paraneoplásico asociado a Ac-anfifisina y cáncer de
Cartas al director
Neurología 2009;24(3):209-216 21593
Tabla 1 Evolución clínica y analítica
tras la dieta sin gluten
Tasa anualizada
de brotes 10 0
EDSS19 10 0
Diarrea Sí No No
Peso (Kg) 58 63 67
RM T2 (n.° de placas) 11 9
ALT (U/l) 60 48 20
Biopsia duodenal
(estadío de Marsh)63b 0
IFN beta 1a
(44 mcg s.c. 3xs) No
A los 6 añosA los 2 añosBasalEvaluación
ALT: alanino transaminasa. EDSS: Expanded Disability Status Scale (escala
ampliada de discapacidad para EM); IFN s.c. 3xs: interferón subcutáneo 3 veces
por semana; RM T2: resonancia magnética en secuencia ponderada T2.
C. Hernández-Lahoz1
S. Rodríguez1
A. Tuñón1
A. Saiz2
E. Santamarta2
L. Rodrigo3
Servicios de 1Neurología, 2Radiología
y3Digestivo
Hospital Universitario Central
de Asturias (HUCA)
Oviedo
Correspondencia:
Carlos Hernández-Lahoz
Servicio de Neurología
Hospital Universitario Central de Asturias
Julián Clavería, s/n
33006 Oviedo
Correo electrónico: carloshlahoz@terra.es
Recibido el 29-9-08
Aceptado el 13-10-08
... Historically, a GFD has occasionally been used in a speculative way to treat MS. There are only anecdotal descriptions of the use of a GFD, targeting a possible beneficial effect, in isolated cases with this disease [35][36][37], and subsequent studies found some benefit from their implementation [38]. ...
Article
Full-text available
Objectives: To analyse the clinical efficacy of a Gluten-Free Diet (GFD) compared with a Regular Diet (RD) in Relapsing-Remitting Multiple Sclerosis (RRMS) patients. Methods: Seventy-two RRMS patients were included into a prospective study. Annual relapse rate (ARR), Expanded Disability Status Scale (EDSS) and lesional activity were compared. Patients were randomly separated according to diet: (GFD, n=36) and (RD, n=36). Follow-up study period was 5.3 ± 1.6 years (median 4.5 years). Results: At the end of the study period, a clear improvement in the EDSS was observed in GFD (1.5 ± 1.4) compared with RD (2.1 ± 1.5) (p=0.001), and lesional activity (MRI) was found in 10 (28%) in GFD, compared to 24 (67%) in RD (p=0.001) [OR: 5.200; (CI95%: 1.901- 14.220)]. Average ARR was lower in GFD (0.4 ± 0.6) compared to RD (0.6 ± 0.6) (NS).
... Anecdotal reports described patients diagnosed with relapsingremitting MS and CD began suffered fewer outbreaks of MS after adhering to a gluten-free diet (Hernández-Lahoz et al., 2009;Meyts et al., 2011). Regarding the prevalence of CD in patients diagnosed with NMO or myelopathy, the literature contains only case reports (Jacob et al., 2005;Meyts et al., 2011). ...
Article
Purpose: Comorbidity of celiac disease with demyelinating diseases of the central nervous system has been reported since the 1960s. The objective of this study was to determine the serological prevalence of celiac disease in the largest series of patients diagnosed with multiple sclerosis, neuromyelitis optica, or myelitis. Methods: A prevalence study was conducted with patients evaluated at Sarah Network of Rehabilitation Hospitals between March 2012 and September 2013. They were previously diagnosed with multiple sclerosis, neuromyelitis optica, or idiopathic myelitis. The serum levels of antibodies against tissue transglutaminase and endomysium were assessed. Results: Of the 379 patients evaluated, 249 (65.70%) were diagnosed with multiple sclerosis, 37 (9.56%) with neuromyelitis optica, and 96 (24.54%) with idiopathic myelitis. Two patients (0.53%), one with multiple sclerosis and other with myelitis, tested positive for both antibodies. Conclusion: Our study do not confirm the relationship between celiac serological antibodies with multiple sclerosis, neuromyelitis optica and inflammatory myelitis of an unknown etiology.
... We have also described(Hernández-Lahoz et al., 2009) the case of a 29-year-old woman suffering from RRMS clinically with recurrent relapses of myelitis at different spinal levels, 10 every year for three years. She had typical MS lesions in brain and spinal cord MRI-scan, oligoclonal IgG bands in CSF and delayed spinal conduction in somatosensory-evoked potentials with normal visual evoked potentials. ...
... CD or gluten sensitive enteropathy, is a chronic systemic autoimmune disorder resulting from in genetically susceptible individuals. Along with enteropathy, diverse extra-intestinal manifestations including neurologic, dermatologic and other autoimmune disorders accompany CD (3,13,(20)(21)(22)(23). ...
Article
Full-text available
Multiple sclerosis (MS) is an autoimmune inflammatory process that affects the central nervous system (CNS). Celiac disease (CD) is a systemic autoimmune disorder of gluten intolerance. Based on the presumed association of MS with multiple autoimmune processes, the coincidence of MS with gluten sensitivity has been investigated with controversial results. Here, we report a known case of MS with mild gastrointestinal symptoms and spontaneous abortions. Thorough paraclimcal evaluations revealed iron deficiency anemia and high titers of tissue transglutaminase antibody (tTG). A small bowel biopsy demonstrated changes compatible with CD, MARSH type 3c. Based on the serologic results and biopsy findings, a diagnosis of CD was established and the patient was instructed to consume a gluten-free diet. Gastrointestinal symptoms abated and her serum levels of tTG normalized, along with improvement in the patient's iron profile dunng follow ups. The combined presence of MS and CD is a rare situation for which previous studies have failed to clarify the existence of any correlation between MS and CD. Thus, further investigation of CD in MS patients with gastroenterological complaints is recommended.
... Chronic gastro-intestinal abnormalities and polyneuropathy were attributed to previous alcohol consumption. Since CD occurs in up to 11% of the patients, together with MS [12][13][14], it cannot also be excluded that the described patient simultaneously suffered from CD and MS. Arguments for the coexistence of both conditions are the CSF and MR findings, improvement of gastrointestinal manifestations and polyneuropathy upon gluten-free diet, and previous reports about the collateral occurrence of both conditions [14]. ...
Article
Full-text available
Due to the similarity in the clinical presentation, morphology, and course, celiac disease (CD) may be mixed up with other immunological disorders, such as multiple sclerosis (MS). In a 43-year-old Caucasian male with a history of diarrhea and colics since young age, progressive sensory disturbances developed since age 18 years. At age 34, he was diagnosed as relapsing-remitting MS upon an inflammatory CSF-syndrome and non-specific white matter lesions and treated with interferon beta-1b during the next 8 years without effect. At age 35, axonal polyneuropathy and ataxia were diagnosed. Despite normal anti-gliadin, endomysial, and transglutaminase antibodies, CD was diagnosed at age 41, based upon the history, polyneuropathy, positivity for HLA-DQ2 and HLA-DQ8, the white matter lesions, and a beneficial response of the gastrointestinal problems and polyneuropathy to gluten-free diet. CD may mimic MS and may be present despite the absence of anti-gliadin, endomysial or transglutaminase antibodies. CD should be considered if there is a gastrointestinal problem, polyneuropathy, and ataxia, even if CSF and MRI findings are suggestive of MS.
Chapter
Im weiten Spektrum chronisch entzündlicher Erkrankungen haben sich naturheilkundliche Ansätze mit Ernährung und Fasten überwiegend der chronischen Polyarthritis und ihr nahestehenden Erkrankungsformen wie der Psoriasisarthritis gewidmet, weniger beispielsweise den Kollagenosen. Ältere und neuere Ansätze sowie die Praxis der Betroffenen weisen der Ernährung – je nach Schule ergänzt bzw. initiiert durch die Fastentherapie – einen hohen Stellenwert in der Entzündungskontrolle zu.
Article
Full-text available
ABSTRACT. Introduction: Multiple sclerosis is a chronic inflammatory autoimmune disorder, characterized by the presence of disse-minated demyelinating lesions in the central nervous system. Gluten not only affects the organism causing celiac disease, but it also intervenes in other pathologies associated with glycoproteins. Gluten can cause neurologic damages through a combination of antibo-dies of crossed-reaction, complex immune diseases and direct toxicity. Some studies show the positive effect of removing gluten from a patient’s diet. Aim: To review scientific literature related to gluten ingestion in multiple sclerosis, and to analyse the evidence that this hypothesis supports. Methods: Bibliographic search in PubMed database. Several search strategies were designed, combining keywords according to the studies that were sought in order to find the highest scientific evidence possible. Results: The cause of neurologic symptoms are not known but it has been suggested that the autoimmunity resulting from the molecular mimicry between gliadin and proteins from the nervous system have a relevant role. Some patients suffering from multiple sclerosis experienced a significant relief of their symptoms after being on a gluten-free diet. Conclusion: There is a possible association between the disruption of the flow of information within the brain and body and gluten. Studied patients may improve or stabilize their cognitive condition with the removal of gluten. Studies reviewed have all shown low-medium evidence as a whole. More studies are needed, specially randomized clinical trials. RESUMEN EN ESPAÑOL: La esclerosis múltiple es un trastorno inflamatorio autoimmune, caracterizado por la presencia de lesiones desmielinizantes diseminadas en el sistema nervioso central. El gluten no sólo afecta al organismo causando la enfermedad celíaca, sino que también interviene en otras patologías asociadas con glicoproteínas. El gluten puede ocasionar lesiones neurológicas por medio de la combina-ción de anticuerpos cros-reactivos, enfermedades inmunes complejas y daño directo. Algunos estudios muestran el efecto positivo de la eliminación del gluten de la dieta de los pacientes. Objetivo: revisar la literatura científica relacionada con el gluten y la esclerosis múlti-ple, y analizar la evidencia que apoya esta posible relación. Métodos: búsqueda bibliográfica en la base de datos PubMed. Se diseñaron varias estrategias de búsqueda, combinando palabras clave de acuerdo con los estudios que fueron hallados, con el fin de obtener la evidencia científica de mayor calidad. Resultados: la causa de los síntomas neurológicos no se conoce, pero se ha sugerido que un pro-ceso autoinmune resultado de un proceso de mimetismo molecular entre la gliadina y las proteínas del sistema nervioso podría tener un papel relevante. Algunos pacientes de esclerosis múltiple experimentan una reducción significativa de sus síntomas tras seguir una dieta libre de gluten. Conclusión: hay una posible asociación entre la disrupción del flujo de información entre cerebro, cuerpo y gluten. Los estudios revisados tienen un grado bajo-medio de evidencia en conjunto. Se precisan más estudios y especialmente ensayos clínicos aleatorizados
Article
Full-text available
Gluten-related disorders are a spectrum of systemic immune mediated conditions that occur at any age in genetically susceptible individuals upon ingesting gluten. Celiac disease and gluten sensitivity are the most important conditions of the spectrum. They may be associated with other autoimmune diseases, such as multiple sclerosis and neuromyelitis optica. Treatment with a gluten-free diet can provide considerable benefits to the patients having both a gluten-related disorder and one of these 2 demyelinating diseases of the central nervous system.
Article
Gluten-related disorders are a spectrum of systemic immune mediated conditions that occur at any age in genetically susceptible individuals upon ingesting gluten. Celiac disease and gluten sensitivity are the most important conditions of the spectrum. They may be associated with other autoimmune diseases, such as multiple sclerosis and neuromyelitis optica. Treatment with a gluten-free diet can provide considerable benefits to the patients having both a gluten-related disorder and one of these 2 demyelinating diseases of the central nervous system. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Article
Full-text available
This article examines associations between gluten, polymorphisms of the major histocompatibility complex, and mucosal pathology representative of the spectrum of gluten sensitivity. Sequences of wheat, rye, and barley prolamins contain recurring tetrapeptide motifs that are predicted to have beta-reverse-turn secondary structure and that, with in vitro assays, appear active. Structural polymorphisms of major histocompatibility complex subloci identify codon switches within the second exon that control the third hypervariable region in the outer domain of the beta chain. Observations of the intestinal response to gluten reveal five interrelated lesions (preinfiltrative, infiltrative, hyperplastic, destructive, and hypoplastic) that are interpretable as cell-mediated immunologic responses. These responses originate in the lamina propria, where a series of antigen-specific inflammatory processes has now been identified. There is no evidence that celiac sprue is a disease of jejunal enterocytes. Furthermore, the role of intraepithelial space lymphocytes in pathogenesis, if relevant, needs further experimental dissection. Also awaiting further definition are polymorphisms of the celiac lymphocyte antigen receptor and their relationship to gliadin oligopeptide(s) and predisposing genes. The nature and basis of nonresponsive celiac sprue require more thoughtful initiatives to elucidate the immunologic mechanism(s) of unresponsiveness and evaluate possible means of reversal. Finally, a more sensible definition of gluten sensitivity (unhampered by qualitative morphological imagery) is ultimately called for in order to accommodate the biomolecular advances addressed in this review.
Article
Full-text available
Coeliac disease (CD) is an enteropathic disorder characterised by a strong association with major histocompatibility complex (MHC) heterodimer HLA-DQ2. It has been suggested that other HLA class I genes in combination with DQ may also contribute to CD susceptibility. The aim of this study was to investigate whether other candidate genes modify the risk of developing different clinical forms of CD. We studied 133 Spanish coeliac patients, divided according to their clinical presentation into typical and atypical groups, and 116 healthy controls. All were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) at HLA-B, DRB1, DQA1, and DQB1 loci and for exon 5 of the MHC class I chain related gene A (MICA). No differences were found in the frequency of the DQA1*0501/DQB1*0201 heterodimer in either group. The risk of typical CD was significantly associated with the DR7/DQ2 haplotype (p(c)=0.02, odds ratio (OR)=3.4, ethiological fraction (EF)=0.4). Extended haplotype (EH) 8.1 (B8/DR3/DQ2) was found to be overrepresented in the atypical form compared with the typical form (p(c)=0.001, OR=4.19, EF=0.56). The trinucleotide repeat polymorphism MICA-A5.1 was found to be increased in the atypical group of patients compared with the typical group (p(c)=0.00006, OR=8.63, EF=0.81). This association was independent of linkage disequilibrium with EH8.1 as this was also found to be increased in EH8.1 negative atypical patients compared with the typical group (p(c)=0.004, OR=6.66, EF=0.56). Our results showed that the risk of developing typical forms of CD was associated with DR7/DQ2 haplotype, and the presence of B8/DR3/DQ2 was significantly increased in atypical patients. In these, the MICA-A5.1 allele confers an additive effect to the DR3/DQ2 haplotype that may modulate the development of CD.
Article
Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.
Article
Multiple sclerosis is the prototype inflammatory autoimmune disorder of the central nervous system and, with a lifetime risk of one in 400, potentially the most common cause of neurological disability in young adults. As with all complex traits, the disorder results from an interplay between as yet unidentified environmental factors and susceptibility genes. Together, these factors trigger a cascade of events, involving engagement of the immune system, acute inflammatory injury of axons and glia, recovery of function and structural repair, post-inflammatory gliosis, and neurodegeneration. The sequential involvement of these processes underlies the clinical course characterised by episodes with recovery, episodes leaving persistent deficits, and secondary progression. The aim of treatment is to reduce the frequency, and limit the lasting effects, of relapses, relieve symptoms, prevent disability arising from disease progression, and promote tissue repair. Despite limited success in each of these categories, everyone touched by multiple sclerosis looks for a better dividend from applying an improved understanding of the pathogenesis to clinical management.
Article
One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
Article
1. The regional cerebral blood flow was studied by SPECT in patients with partial epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2. Both a qualitative visual interpretation and a semiquantitative analysis of SPECT was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ serum concentrations were assayed. 3. After therapy, in three patients with focal epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with respect to the side of the epileptic focus in the opposite hemisphere. No morphologic changes were detected at MRI in the cerebral or cerebellar remote hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the corticopontocerebellar pathways and on the corticocallosal connections.