Anti-tumor necrosis factor alpha therapy (adalimumab) in Rasmussen's encephalitis: An open pilot study.
Rasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug-resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology.



We report an open-label study evaluating the efficacy and the safety of anti-TNF-α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects.



Adalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow-up was for a median period of 18 months (range 9-54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated.



Our study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results.
Clinical Neurophysiology and Epileptology Department, Timone Hospital, APHM, Marseille, France.
Stanislas
S
Lagarde
Henri Gastaut Hospital, Marseille, France.|Pediatric Neurology Department, Timone Hospital, APHM, Marseille, France.
Nathalie
N
Villeneuve
Clinical Neurophysiology and Epileptology Department, Timone Hospital, APHM, Marseille, France.
Agnès
A
Trébuchon
Neurology Department, Timone Hospital, APHM, Marseille, France.
Elsa
E
Kaphan
Henri Gastaut Hospital, Marseille, France.|Pediatric Neurology Department, Timone Hospital, APHM, Marseille, France.
Anne
A
Lepine
Clinical Neurophysiology and Epileptology Department, Timone Hospital, APHM, Marseille, France.
Aileen
A
McGonigal
Pediatric Neurology Department, "Gui de Chauliac" Hospital, Montpellier, France.
Agathe
A
Roubertie
Pediatric Neurology Department, Clocheville Hospital, Tours, France.
Marie-Anne J
MA
Barthez
Pediatrics Department, La Reunion South Hospital, La Reunion, France.
Valérie
V
Trommsdorff
Pediatric Neurology Department, Brest Hospital, Brest, France.
Jérémie
J
Lefranc
Pediatrics Department, André Mignot Hospital, Le Chesnay, France.
Samer
S
Wehbi
Pediatric Neurology Department, Lyon Public Hospital, Lyon, France.
Vincent
V
des Portes
Henri Gastaut Hospital, Marseille, France.
Virginie
V
Laguitton
Pediatric Immunology-Hematology and Rheumatology Unit and IMAGINE Institute, "Necker-Enfants Malades" Hospital, APHP, Paris, France.
Pierre
P
Quartier
Pediatric Neurosurgery Department, Timone Hospital, APHM, Marseille, France.
Didier
D
Scavarda
Division of Public Health, Timone Hospital, APHM, Marseille, France.|Brain Dynamic Institute, INSERM UMR 1106 and Aix-Marseille University, Marseille, France.
Bernard
B
Giusiano
Pediatric Neurology Department, Timone Hospital, APHM, Marseille, France.
Mathieu
M
Milh
Pediatric Neurosurgery Department, Ophthalmologic Foundation "A. de Rothschild", Paris, France.
Christine
C
Bulteau
Pediatric Neurosurgery Department, Timone Hospital, APHM, Marseille, France.
Fabrice
F
Bartolomei
D000068879:Adalimumab / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004569:Electroencephalography; D004660:Encephalitis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009483:Neuropsychological Tests; D010865:Pilot Projects; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014741:Video Recording; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
Adalimumab; Anti-tumor necrosis factor alpha; Epilepsy; Inflammation; Rasmussen encephalitis