Anthrax meningoencephalitis: Appendices

Douglas J. Lanska, M.D., M.S., M.S.P.H. 5-11-02

Veterans Affairs Medical Center

Great Lakes VA Healthcare System

Tomah, WI;

Department of Neurology

University of Wisconsin

Madison, WI

Correspondence:

Douglas J. Lanska, M.D.

Chief of Staff

VA Medical Center

500 E. Veterans Street

Tomah, WI 54660

608-372-1778

608-372-1654 (FAX)

[email protected] Anthrax Meningoencephalitis: Appendix 1

Translation of Contribution to the Knowledge of Anthrax Meningitis By Ernst von Czyhlarz

Translation by Bernd Remler, M.D. Medical College of Wisconsin, Milwaukee. Page 3

CONTRIBUTION TO THE KNOWLEDGE OF ANTHRAX MENINGITIS

By Ernst von Czyhlarz

[Translation by Bernd Remler, M.D., Medical College of Wisconsin, Milwaukee. From:

Czyhlarz E. Beitrag zur Lehre von der der Milzbrandmeningitis. Wiener Klinische

Wochenscrift 1916;25:768-769.]

The first author who reported a likely case of anthrax meningitis was E. Wagner (1874).

He described exclusively patients who had come to autopsy. In the following years,

additional cases were reported predominantly by pathologists, in particular forensic

pathologists (Eppinger, von Hofmann, Kundrat, R. Paltauf, Risel, Kolisko, Schmorl). In all

likelihood, this reflects the circumstance that anthrax meningitis causes unexpected and

rapid death due to intrameningeal bleeding in a characteristic pattern.

The limited knowledge and interest afforded anthrax infections of the central nervous

system is further reflected in A. Nicolaier’s quote in his standard textbook “The German

Clinic” from 1903: “The brain shows mostly smaller hemorrhages, which are also not

uncommon in the meninges. In addition, small softening spots (translator: necrotic

areas?) are seen.”

There is almost no published information on the clinical course of cerebral anthrax, in

particular anthrax meningitis. Its prognosis is generally considered poor, even in the best

circumstances. Noteworthy is a contribution by Pollak, who in one case succeeded to

demonstrate anthrax bacilli in the cerebrospinal fluid in vivo. Thus, the diagnosis was Page 4

established before the patient died and came to autopsy.

As already mentioned, most contributions on this topic were made by forensic

pathologists. Kolisko stated in his chapter in the Handbook of Expert Medical Evaluation

(ed: Dittrich): “There are cases of anthrax progressing rapidly to death without the

patient or his peers having any indication of the grave nature of the infection and in

whom only autopsy proved the cause of death by anthrax. In such fulminant cases, the

cause of sudden death is usually an intrameningeal hemorrhage.” The intrameningeal

hemorrhages caused by anthrax are reported to have a highly characteristic feature with

regard to their distribution pattern. Either the extravasation is very regularly spread

across the entire brain – a feature not seen with any other cause of intrameningeal

hemorrhaging - or the blood is pooling on the cerebral surface, particularly over the

convexities. In very rare cases, the parenchyma can be involved in such a fashion that

numerous capillary hemorrhages are seen in the cortex, the ganglia and the white

matter.

As a path of infection, the nasal air passages are the likely route. This has been

anatomically and histologically proven in Risel’s and Schmorl’s cases. Page 5 CASE DESCRIPTION:

K. R. is a 24-year-old, unmarried, unskilled laborer. She was admitted on 02/19/40.

Past Medical History: She has always been healthy. Three days before admission she

developed an acute illness, with vomiting, severe headaches and chills. Several hours

after the onset of her illness she became somnolent.

The examination upon admission showed her to be a well-developed female of average

build. The skin was normal. She was deeply obtunded. The pulse was 96 and the

temperature 39.8 Celsius. She either did not respond to stimulation or mumbled

unintelligibly. The neck was retroflexed and stiff. The left upper extremity appeared

paralyzed and there was also apparent weakness in the left lower face and the left lower

extremity. The fundoscopic examination was unremarkable.

The clinical picture on the following day (02/20) was grossly unchanged.

On 02/21 the patient underwent a lumbar puncture, which yielded hemorrhagic

cerebrospinal fluid. The bacteriologic examination (Professor Stoerk) yielded numerous,

large, Gram positive anthrax-like rods. The cerebrospinal fluid cultures grew anthrax

bacilli. The Wassermann reaction was strongly positive in the CSF, but negative in

venous blood.

On 02/22 the patient’s temperature dropped into the normal range of 36.8. During the

preceding days the temperature had been elevated between 38.5 and 39.5. During the

afternoon of 02/22 the temperature again rose to 38, but dropped into the normal range Page 6

by the evening and remained normal throughout the further course. Already by 02/22 the

patient’s sensorium had improved to nearly normal and she only complained of

headaches.

On 02/23 she appears cognitively normal. Her headaches have resolved. The left-sided

hemiparesis is now obvious and most pronounced in the left upper extremity.

A repeat lumbar puncture on 02/24 yielded clear spinal fluid. The bacteriologic

evaluation and the Wassermann reaction were negative.

In the further course the patient showed persistent left-sided weakness, which only

improved in the leg. The arm remained nearly completely paralyzed with early

contractures. After many months, the left lower facial weakness also persists nearly

unchanged.

The Wassermann reaction in the blood remained normal during the entire observation

period and was also negative in the last spinal fluid sample obtained on 03/01.

Our patient had bacteriologically confirmed anthrax meningitis and anthrax encephalitis,

with spontaneous resolution, but a residual left hemiparesis. Its causation by an

intracerebral hemorrhage appears beyond doubt. It is difficult to imagine that focal

destruction of the cortical surface by the intrameningeal hemorrhage was causing the

motor deficits. The absence of irritative phenomena would further support an

intraparenchymal cause of the weakness.

I was unable to identify another nonfatal case of anthrax meningitis in a detailed review Page 7

of the literature. However, in discussing this patient with colleagues, I heard about two

similar cases. Hofrat Kolisko graciously told me about a case that another colleague had

observed. A second patient was seen by Dr. Bylof, who, at the time, practiced in Graz. I

gratefully acknowledge his personal communication. His patient worked as a stable

hand. Clinically, he presented with acute onset, severe headaches and other symptoms

suggestive of a severe meningitis. Following a lumbar puncture, which yielded blood-

tinged fluid and anthrax bacilli, the patient improved surprisingly quickly and recovered.

Thus, this patient’s course was analogous to ours. Clinical improvement following lumbar

puncture would suggest that this procedure was of benefit in both patients. However, the

small number of cases does not support firm conclusions in this regard. Nonetheless,

our experience indicates that a relatively benign and short lasting form of anthrax

meningitis exists that has a cyclical course (translator: it is not clear what the author

means by cyclical course). Whether this form of anthrax meningitis is accompanied by

anthrax sepsis is uncertain, but probable, considering the findings in epidemic

meningitis.

The residual hemiparesis in our patient, as pointed out, suggests a hemorrhage into the

internal capsule. We, therefore, propose that anthrax infection of the central nervous

system not only causes petechial hemorrhages, which are mostly asymptomatic, but

also larger, intraparenchymal hemorrhages that can cause focal neurologic deficits.

A new observation in my case is a strongly positive Wassermann reaction in the

cerebrospinal fluid at the height of her neurological illness. This resolved quickly and in

parallel with her rapid clinical improvement. Page 8

Anthrax Meningoencephalitis: Appendix 2

CSF results in anthrax meningoencephalitis by survival status

Douglas J. Lanska, M.D.

Veterans Affairs Medical Center Great Lakes VA Healthcare System Tomah, WI; Department of Neurology University of Wisconsin Madison, WI Page 9

FIGURE LEGEND: CSF results in anthrax meningoencephalitis by survival status. The figure shows results for glucose, protein, red cells, and white cells from the initial lumbar puncture in cases with and without survival (designated “A” for alive and “D” for deceased, respectively). Given the small number of cases with survival, individual results for this group are plotted (horizontally “jittered” as necessary to allow visualization of each point). For deceased cases, results are summarized with Tukey box plots, with the “box” showing the 25th percentile, median, and 75th percentile values, the “whiskers” showing the 10th and 90th percentiles, and individually plotted (“unjittered”) values showing the extreme values.