Ausgewählte Publikationen

Retinal ganglion cell loss in neuromyelitis optica: a longitudinal study

J Neurol Neurosurg Psychiatry. 2018 Jun 19. pii: jnnp-2018-318382. doi: 10.1136/jnnp-2018-318382

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory conditions of the central nervous system and an important differential diagnosis of multiple sclerosis (MS). Unlike MS, the course is usually relapsing, and it is unclear, if progressive neurodegeneration contributes to disability. This study clearly shows GCIP loss independent of ON attacks in aquaporin4-antibody-seropositive NMOSD. [mehr...]

[18F]-THK5351 PET Correlates with Topology and Symptom Severity in Progressive Supranuclear Palsy

Front. Aging Neurosci. | doi: 10.3389/fnagi.2017.00440

[18F]-THK5351 is a novel PET-ligand that may afford in vivo visualization and quantification of tau-related alterations. We investigated binding characteristics of [18F]-THK5351 in patients with clinically diagnosed PSP and correlate tracer uptake with clinical findings. [mehr...]

No need for NMDA receptor antibody screening in neurologically asymptomatic patients with ovarian teratomas.

J Neurol. 2017 Dec 22. doi: 10.1007/s00415-017-8717-3. [Epub ahead of print]

No need for NMDA receptor antibody screening in neurologically asymptomatic patients with ovarian teratomas [mehr...]

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders

Mult Scler. 2016 Oct 6. pii: 1352458516671203. [Epub ahead of print]

Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD [mehr...]

Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration

J Neurol. 2017 Jan;264(1):139-151. doi: 10.1007/s00415-016-8333-7. Epub 2016 Nov 14.

Antibodies against conformation-dependent epitopes of myelin-oligodendrocyte-glycoprotein (MOG-abs) are present in subgroups of neuromyelitis optica spectrum disorder (NMOSD), recurrent optic neuritis (rON), multiple sclerosis (MS), and anti-NMDAR encephalitis. Using optical coherence tomography (OCT) we assessed whether MOG-abs might serve as potential marker of retinal axonal degeneration. [mehr...]

Interdisciplinary Risk Management in the Treatment of Multiple Sclerosis

Dtsch Arztebl Int 2016; 113(51-52): 879-86; DOI: 10.3238/arztebl.2016.0879

The growing number of drugs used to treat MS demands great efforts to minimize the potential risks. To this end, interdisciplinary risk management plans are essential. Here we describe the type and extent of risks, the measures needed for prevention/early detection, and provide practical advice for the necessary monitoring. [mehr...]

CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis.

Ann Neurol. 2016 Aug;80(2):294-300. doi: 10.1002/ana.24715.

We investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA4-blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical magnetic resonance imaging (MRI) changes (radiologically isolated syndrome). Two courses of ipilimumab were each followed by a clinical episode of MS, 1 of which was accompanied by a massive increase of MRI activity. Brain biopsy confirmed active, T-cell type MS. Quantitative next generation sequencing of T-cell receptor genes revealed distinct oligoclonal CD4(+) and CD8(+) T-cell repertoires in the primary melanoma and cerebrospinal fluid. Our results pinpoint the coinhibitory molecule CTLA4 as an immunological checkpoint and therapeutic target in MS. Ann Neurol 2016;80:294-300. [mehr...]

Alemtuzumab and Multiple Sclerosis: Another Note of Caution.

JAMA Neurol. 2016 Apr 4. doi: 10.1001/jamaneurol.2016.0259. [Epub ahead of print]


Cryopyrin-associated periodic fever syndrome manifesting as Tolosa-Hunt syndrome

Cephalalgia. 2016 Feb 3. pii: 0333102416629239. [Epub ahead of print]

Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low-penetrance mutation (Q703K) of the cryopyrin/NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome. This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin-associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients. [mehr...]

Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses

Ann Neurol. 2015 Nov 4. doi: 10.1002/ana.24554

Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. We were able to show, that particularly myelitis and bilateral optic neuritis have poor remission rates. However, escalation of attack therapy improves outcome. [mehr...]

Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations.

Neurol Neuroimmunol Neuroinflamm. 2015 May 14;2(4):e109. doi: 10.1212/NXI.0000000000000109. eCollection 2015.

We evaluated the frequency of the cryoporin/NLRP3 low-penetrance mutations V198M and Q703K in patients who reported at least 2 symptoms compatible with cryopyrin-associated periodic syndromes (CAPS) and characterized the phenotype in mutation-positive patients. Seventeen patients (16%) tested positive for either of the 2 mutations (V198M: n = 2; Q703K: n = 15). Eleven patients (65%) had severe headache syndromes. Six of these 11 patients were diagnosed with migraine. Nine patients (53%) had a concomitant diagnosis of multiple sclerosis (MS). In 3 patients, we identified additional family members with the respective mutation as well as the diagnosis of MS. Severe recurrent cranial nerve (CN) affection was the hallmark feature in 7 of the 8 (88%) non-MS mutation carriers. Brain MRI showed abnormalities in all but 2 patients (88%) and detected CN inflammation in 4 patients. Interleukin-6 was elevated in the CSF of 2 patients in the non-MS cohort during acute CAPS episodes with severe CNS inflammation. 5 of 9 treated patients (56%) responded to anti-interleukin-1 therapy. CAPS constitute rare but treatable and commonly misdiagnosed autoinflammatory syndromes. Our data expand the spectrum of CAPS-associated neurologic manifestations. They also broaden our concept of autoimmunity and autoinflammation by linking CAPS and MS. [mehr...]

Immunotherapies for multiple sclerosis : Review and update

Internist (Berl). 2015 Feb 28

In this review particular attention is given to the risks of new therapies, monitoring, and on special aspects needing attention when changing treatments. [mehr...]

Histopathology and clinical course of MOG-antibody-associated encephalomyelitis.

Ann Clin Transl Neurol. 2015 Mar;2(3):295-301. doi: 10.1002/acn3.164. Epub 2015 Jan 14.

We present histological, MRI, and clinical features of an adult patient with relapsing encephalomyelitis and antibodies against myelin oligodendrocyte glycoprotein (MOG). Furthermore, we report molecular details of the recognized epitope that is specific for human MOG. A brain biopsy revealed multiple sclerosis (MS)-type II pathology. Some features overlapped with both MS and neuromyelitis optica spectrum disorders (NMOSD), whereas others were distinct from both MS and NMOSD. Immunoadsorption and rituximab induced clinical stabilization. This case contributes a new, so far missing link in the emerging spectrum of MOG-antibody-associated encephalomyelitis. [mehr...]

Multiple sclerosis-like lesions and type I interferon signature in a patient with RVCL.

Neurol Neuroimmunol Neuroinflamm. 2014 Dec 23;2(1):e55. doi: 10.1212/NXI.0000000000000055. eCollection 2015.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare late-onset autosomal dominant systemic microvascular disease due to C-terminal truncation mutations in the three prime repair exonuclease 1 gene, TREX1.1 Patients present with varying degrees of progressive bilateral vision loss, renal impairment, and neurologic symptoms. Cerebral MRI shows either confluent tumorlike signal alterations or multiple small white matter lesions.2,3 Herein we demonstrate a case of RVCL caused by a novel TREX1 mutation with distinct lesions on cerebral MRI and type I interferon (IFN) activation. [mehr...]

Predictors for multiple sclerosis relapses after switching from natalizumab to fingolimod.

Mult Scler. 2014 May 19. pii: 1352458514533398.

The objective of this paper was to identify risk factors for recurrence of relapses after switching from NAT to fingolimod (FTY) in relapsing-remitting multiple sclerosis (RRMS). [mehr...]

Late-onset neutropenia during long-term rituximab therapy in neuromyelitis optica

Mult Scler Relat Disord. 2014 Mar;3(2):269-72. doi: 10.1016/j.msard.2013.08.001.

Late-onset neutropenia (LON) has been described as a side effect of rituximab (RX) therapy in patients with rheumatological and/or haematooncological diseases but not neuromyelitis optica (NMO). We describe a 71-year old female patient, who had NMO for 22 years, had been treated with RX monotherapy five times before she developed severe neutropenia (IV) 3 months after the last RX infusion. [mehr...]

Bridging, switching or drug holidays – how to treat a patient who stops natalizumab?

Therapeutics and Clinical Risk Management. October 2013(9) 361 - 369


MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis.

Brain. 2013 Jun;136(Pt 6):1778-82. doi: 10.1093/brain/awt101

We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. [mehr...]


Prof. Dr.

Reinhard Hohlfeld


Prof. Dr.

Martin Kerschensteiner



Prof. Dr.

Tania Kümpfel