Neurology -- Correspondence for Mathew et al., 68 (12) 900-905

Correspondence published:

Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis: Harald Prüss, Rolf Zschenderlein, Konstantin Prass (24 May 2007)

Reply from the authors: Josep Dalmau, Rose Marie Mathew, MD (24 May 2007)

Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis 24 May 2007

Harald Prüss,
Department of Neurology, Charité – University Medicine Berlin
Schumannstrasse 20/21, 10117 Berlin, Germany,
Rolf Zschenderlein, Konstantin Prass
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Re: Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis

harald.pruess{at}charite.de Harald Prüss, et al.

In their recent article, Mathew et al report six cases of Ma2-associated encephalitis with microscopic neoplasms of the testis found only after orchiectomy. [1] We encountered a patient with atypical Parkinsonism and massive rigidity due to occult testicular cancer whose case adds to this rare condition. [2]
The 66-year-old man developed disorientation, psychomotor agitation, and fever. Over three months, he developed an akinetic-rigid syndrome, mask- like facies, bilateral ptosis, slow pupillary response, primitive reflexes, and absent leg reflexes. He had a low-grade fever, tachycardia, and profuse sweating.
Positive anti-Ma2 antibodies together with the compatible neurological and MRI findings proved a paraneoplastic origin. Endoscopy, FDG-PET, repeated body CT, and bone marrow biopsy revealed no neoplastic changes. Tumor markers AFP and beta-HCG were normal. Testicular ultrasound revealed homogeneous echo pattern, no atrophy, microcalcifications, or masses suspicious for malignancy.
At the time of presentation in 2001, all previously reported cases with anti-Ma2 encephalitis had testicular neoplasms. [3] Because of life-threatening neurological deterioration, the patient’s wife consented to bilateral orchiectomy. In line with other reports of improvement after tumor resection in Ma2-encephalitis,[4]symptoms improved including spontaneous eye opening, increasing alertness and communication. The rigidity of all extremities was markedly reduced and most primitive reflexes disappeared. The patient had prolonged stabilization but died from pneumonia 18 months later.
The original pathological evaluation was negative for testicular malignancies but review using placental-like alkaline phosphatase (PLAP)- stained slides verified multiple bilateral microscopic intratubular germ- cell neoplasia.
According to Mathew et al, our patient fulfilled only three of the five criteria proposed for orchiectomy decision: 1) anti-Ma2 antibodies together with clinical features compatible with Ma2-encephalitis; 2) life -threatening deterioration of the neurological deficits; 3) absence of other tumors. The patient failed to meet the criteria 4) age <50 years and 5) testicular abnormalities.
Mathew et al underscore the high tumor- specificity of the well-characterized anti-Ma2 antibodies. Secondly, even in patients without a history of cryptorchidism, atrophy, testicular enlargement, or microcalcifications, Ma2 antibodies together with the neurological symptoms might--in exceptional cases--prompt consideration of orchiectomy. Thirdly, the threshold of age of 50 years should be reconsidered in view of our patient.
References
1. Mathew RM, Vandenberghe R, Garcia-Merino A et al. Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis. Neurology 2007;68:900-905.
2. Prüss H, Voltz R, Flath B et al. Anti-Ta associated paraneoplastic encephalitis with occult testicular intratubular germ-cell neoplasia. JNNP 2007;78:651-2.
3. Voltz R, Gultekin SH, Rosenfeld MR, et al. Serologic marker of paraneoplastic limbic and brainstem encephalitis in patients with testicular cancer. NEJM 1999;340:1788-95.
4. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004;127:1831-1844.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 24 May 2007

Josep Dalmau,
University of Pennsylvania
Department of Neurology, 3 W Gates, 3400 Spruce Street, Philadelphia, PA 19104,
Rose Marie Mathew, MD
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Re: Reply from the authors

josep.dalmau{at}uphs.upenn.edu Josep Dalmau, et al.

Dr. Prüss et al describe a 66-year-old man with anti- Ma2 associated encephalitis without evidence of cancer who underwent bilateral orchiectomy revealing a bilateral intratubular germ-cell tumor. Based on this single case, the authors suggest modifying two of the five criteria for orchiectomy that we utilized for patients with anti-Ma2 encephalitis without evidence of a tumor.[1]
Specifically, the authors suggest performing blind bilateral orchiectomies in patients without ultrasound abnormalities, regardless of the patients’ age. As noted by Prüss et al, their patient is exceptional and therefore not appropriate to develop a rigid and rather extreme recommendation.
The reasons that led us to recommend orchiectomy in our six patients, included: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits; 3) age <50 years; 4) absence of other tumors; and 5) new testicular abnormalities or ultrasound evidence of microcalcifications. These criteria derived from our experience with 46 patients, 25 younger than 50 years (all men) and 21 older than 50 years (8 men) and the distribution of tumors related to age (see supplemental data of our manuscript).[1]
While all men younger than 50 had germ-cell tumors (24 in testis and 1 extragonadal), none of the patients older than 50 had testicular tumors. If bilateral orchiectomies were performed in patients fulfilling our criteria but older than 50, a substantial number of errors would be made.
Furthermore, we stated that,“If the ultrasound is normal and there are no risk factors for a tumor, and the patient develops progressive or life-threatening neurological complications, a blind unilateral orchiectomy should be considered and if negative, a partial or total contralateral orchiectomy may be necessary” and “recommendations based on patient’s age should be taken cautiously.”[1]
In today’s medical environment, many clinical decisions are based on flow charts and algorithms. While this simplifies decision making, there is no substitute for good clinical judgment. Prüss and et al utilized good judgment when they proceeded with orchiectomy after extensive evaluations and in the face of progressive neurological deterioration.
However, it would be wrong to generalize this single case experience. We must emphasize that our proposed criteria for orchiectomy are meant to provide a framework from which to make individualized clinical decisions.
Disclosure: The authors report no conflicts of interest.