Varicella and Acute Cerebellar Ataxia A. C.
Boudewijn Peters, MD; Jan Versteeg, MD; Jan Lindeman, MD; Gerard
\s=b\ In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism. (Arch Neurol 35:769-771, 1978)
Neurolatively ogical complicationschickenpox.
are rel¬ in Acute cerebellar ataxia is the most frequent of neurological syndromes in these cases, especially in children.1 No anatomicopathological correlates are available for this cerebellar syndrome since virtually all patients recover.
rare
Although an immune-mediated parainfectious or postinfectious pro¬
in varicella-associated cerebellar ataxia is assumed to be opérant, the inflammatory nature of some cases of varicella meningoencephalitis makes a single causal mechanism doubtful.2 The demonstration of varicellazoster virus antigen in the CSF of two patients with cerebellar ataxia may
cess
Accepted
for publication Jan 31, 1978. From the Departments of Neurology (Dr Peters), Neuropathology (Dr Bots), and Pathology (Dr Lindeman) and the Laboratory of Medical Microbiology (Dr Versteeg), State University, Academic Hospital, Leiden, The Netherlands. Reprint requests to Department of Neurology, State University, Academic Hospital, Leiden, The Netherlands (Dr Peters).
contribute to the
pathogenesis.
T. A. M. Bots, MD
understanding of
MATERIALS AND METHODS Antisera Antiserum to varicella-zoster virus
was
tissue in the indirect immunofluorescent test, the serum was adsorbed with liver powder and A,B, 0, and Rh antigens from human blood. The specificity and activity of the pooled serum was tested on tissue culture. No fluorescence was observed in uninfected cell cultures. Neither was any fluorescence observed in slides from cases of aseptic meningitis of other cause, for example, coxsackie virus, echovirus, and mumps. Additional controls were performed ac¬
cording to Sternberger.4 Antirabbit -globulin was prepared by immunizing goats with purified rabbit globulin. The antibody titer and the speci¬ ficity of the reaction were tested in immunodiffusion plates. After conjugation with fluorescein isothiocyanate the sera were adsorbed with liver powder and lyophilized in 1-ml aliquots. CSF Cytology and Immuno¬ fluorescent Staining Techniques The CSF
was
obtained was
The next milliliters were used for slides by means of the Sayk sedimentation technique adapted by Bots et al5 One slide was stained with MayGrünwald-Giemsa for cytologie examina¬ tion. The remaining slides were air-dried, fixed in cold acetone, and used immediate¬ ly or stored at —20 °C. Slides were treated with antisera and control sera for 60 minutes at 37 °C, washed in buffered saline pH 7.2, and subsequently treated with antirabbit conjugate for 30 minutes. After washing in phosphate-buffered sa¬ line, a drop of tris-buffered glycerine pH 9.9s was applied and the slide covered with
preparing
prepared by immunizing three rabbits with purified viral antigen mixed with Freund's complete adjuvant. The antigen used was prepared by alkaline extraction3 of in¬ fected human diploid lung fibroblasts. To overcome nonspecific binding with human
ture. The first 2 ml
investigations (blood cell count and differ¬ ential cell count, protein, glucose) by stan¬ dard laboratory procedures.
by lumbar punc¬ used for routine
a
coverglass.
Positive and negative control slides were included in the test. Fluorescence was viewed in dark-field, a high-pressure mer¬ cury lamp being used as a source of ultravi¬ olet light.
ComplementFixing Antibody Testing Paired serum samples were examined for complement-fixing antibodies against mumps, Sendai, coxsackie viruses A and B, echovirus, herpesvirus hominis, cytomegalovirus, and varicella-zoster virus. Routine laboratory investigations in¬ cluded hemogram, complete blood cell count, urinalysis, and determinations of ESR, blood glucose, BUN, creatinine, calcium, phosphorus, uric acid, total protein and albumin, cholesterol, and alkaline
phosphatase.
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Summary
of
Laboratory
Data
Virological Studies
CSF Examination
Lumbar Puncture Day 9*
Case 1 Case 2
"Day
1
Day
=
8
WBC per cu mm
15
Protein,
Cytology Viral infection Nonspecific cell irritation
mg/100 ml
19 37
IgG, mg/100 ml
1.9
Complement-Fixing Titers for Varicella-Zoster > 256 > 256
Immunofluorescent Staining CSF Cells for Virus Antigens Positive for Varicella-zoster Varicella-zoster
on
onset of rash.
Skull roentgenograms and additional EEGs were obtained in both patients.
REPORT OF CASES Case 1.—A 21-month-old boy developed a generalized vesicular exanthema, charac¬ teristic for chickenpox. The patient was afebrile. After three days the cutaneous lesions had predominantly reached the
stage of encrustation. Five days after the appearance of the rash the parents noticed spontaneous tremor-like movements of head, trunk, and arms. The next day a rapid deterioration of
gait was observed, progressing to complete inability to walk. On admission, eight days after the onset of the eruption, the boy was still afebrile. The skin showed widespread crusts. The patient was not able to stand or sit and was irritable and whimpering. The marked ataxic symptoms of trunk and extremities and the intermittent head tremor were not accompanied by other neurological abnormalities. Eight weeks after appearance of the rash the patient was
asymptomatic.
The CSF and virological investigations are summarized in the Table. On admission the complement-fixing titer against vari¬ cella-zoster virus had already reached a maximum level; no further rise could be observed. Immunofluorescence with antivaricellazoster serum by the indirect method on CSF cells was positive, showing different stages of nuclear and cytoplasmic involve¬ ment.
On cytologie examination the CSF showed a marked pleocytosis consisting of about equal numbers of monocytes and lymphocytes. A number of monocytes had cloverleaf-shaped metaplastic nuclei. The lymphoid cells showed polymor¬ phism and a remarkable basophilia of the cytoplasm. Some transitional forms to monocytes and plasma cells were seen. No macrophages were present. The metasplasia of the monocytes together with the polymorphism of the lymphoid cell series suggest a viral infection. Case 2.—Four days after the eruption of a generalized vesicular rash a 5-year-old
Positive fluorescence in CSF cells with antivaricella-zoster serum by the indirect method showing different stages of nuclear and cytoplasmatic involvement in case 1 (fluorescein isothiocyanate, 600).
boy complained of headache, accompanied with vomiting, sleepiness, and a fever of 1.6 °C; he was listless and irritable. The next day he developed a rapidly progress¬ ing gait disturbance, and his speech was noticed to be indistinct and slurred. On admission, seven days after appear¬ ance of the rash, the boy was afebrile. He was covered with crusts of various stages. The patient was noncooperative and whimpering. He was unable to sit, stand, or walk without support. A marked ataxia of trunk and extremities and a dysarthric speech completed the clinical picture. The CSF and virological studies are summarized in the table. On admission the complement-fixing titer against varicellazoster virus had already reached a maxi¬ mum level; no further rise could be observed. Indirect immunofluorescence on CSF cells with a specific antivaricella-zoster serum was positive. The insufficient quali¬ ty of the slide made for cytologie examina¬ tion of the CSF allowed only the conclusion of a nonspecific cell irritation. Results of routine laboratory tests were unremark¬ able. An EEG performed on the sixth day of admission was normal. The patient was discharged 21 days after appearance of the rash with only minimal impairment of coordination. COMMENT
The diagnosis of varicella-asso¬ ciated cerebellar ataxia in both pa-
tients was confirmed by the findings of very high titers of complementfixing antibodies in paired sera. The moderate mononuclear CSF pleiocytosis, suggesting the presence of viral infection, was confirmed by cytologie examination and by immunofluorescent staining of CSF cells with a specific antivaricella-zoster serum that showed a strong, green fluorescence, indicating different stages of nuclear and cytoplasmatic involvement (Figure). Essential data are summarized in the Table. The causative agent in varicella (chickenpox) and herpes zoster (shin¬ gles) is identical: varicella-zoster vi¬ rus. Complications of the respective diseases as they affect the CNS are
widely divergent.2 Pathogenesis in both types of CNS diseases is only partially known. In CNS disease complicating herpes zos¬
a direct viral invasion of the CNS is generally assumed.2 7S Viral isola¬ tions from brain tissue and electron microscopic demonstration of inclu¬ sions and viral particles in neurons and glia have been documented.7 In herpes zoster-associated CNS diseases the virus has been detected in CSF71" and in one case the varicellazoster antigen has been shown in CSF." In CNS complicating varicella
ter
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there are no reports of viral isolation from CNS tissue or CSF. Inclusion bodies have been observed in brain tissue in only one instance.12 Cases of fatal varicella in which there is widespread and overwhelm¬ ing infection by the varicella agent also fail to provide convincing proof of direct CNS invasion." An immunemediated process in varicella-asso¬ ciated meningoencephalitis has been postulated, based on pathological sim¬ ilarities between some cases of vari¬ cella encephalomyelitis and animals with experimental allergic encephali¬ tis.2 Griffith et al,14 in reviewing their varicella cases, stated that in virtually all instances one or another hallmark
of immune-mediated
postinfectious encephalomyelitis lacking. The pathological picture in some was
documented cases of varicella-asso¬ ciated encephalitis showed compo¬ nents, such as perivascular infiltrates, inflammatory infiltration of the leptomeninges, inclusion bodies in brain tissue, which are compatible with a direct viral invasion.1215 Therefore, evidence is lacking to postulate either a direct viral or an immune-mediated process as the single causal mecha¬ nism in varicella encephalitis or cere¬ bellar ataxia.2 To the best of our knowledge nei¬ ther the isolation of varicella-zoster virus nor the demonstration of vari¬ cella-zoster antigens in CSF cells in
of varicella-associated cerebellar ataxia (or meningoencephalitis) have been reported. Demonstration of viral antigens in CSF cells have been employed before and can be consid¬ ered as evidence for viral meningoen¬ cases
cephalitis.16"18 The data presented above appear to
constitute strong contributive evi¬ dence to assume a causal relationship between varicella cerebellar ataxia and direct viral invasion of the CNS. A definite approach to establish a direct viral invasion as the pathogenic factor would require the demonstration of varicella-zoster virus in the cerebellar
parenchyma.
References 1. Appelbaum E, Rachelson MH, Dolgopol VB: Varicella encephalitis. Am J Med 15:223-230, 1953. 2. McKendall RR, Klawans HL: Nervous system complications of varicella-zoster virus, in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam, North-Holland Publishing Co, 1978, vol 34, pp 161-184. 3. Hallauer C, and Kronauer G: Extraction of cell-associated virus without damage of the culture. Arch Gesamte Virusforsch 15:433-440, 1965. 4. Sternberger L: Immunocytochemistry. Englewood Cliffs, NJ: Prentice Hall, 1974, p 53. 5. Bots GTAM, Went LN, Schaberg A: Results of a sedimentation technique for cytology of cerebrospinal fluid. Acta Cytol 8:234-241. 1964. 6. Mrenova M, Albrecht P: Stabilization of fluorescence in preparates treated by fluorescent antibody technique. Nature 212:1256-1257, 1966.
7. McCormick WF, Rodnitzky RL, Schoket SS, al: Varicella-zoster encephalomyelitis: A morphologic and virologic study. Arch Neurol 21:559-570, 1969. 8. Hogan EL, Krigman MR: Herpes zoster myelitis: Evidence for viral invasion of spinal cord. Arch Neurol 29:309-313, 1973. 9. Gold E: Serologic and virus-isolation studies of patients with varicella or herpes-zoster infection. N Engl J Med 274:181-185, 1966. 10. Joncas J, Lussier G, Podeski MO, et al: Zoster encephalitis: A case report. Can J Public Health 59:484-486, 1968. 11. Shoji H, Koya M, Ogiwara H: Meningitis associated with herpes zoster. J Neurol 213:269\x=req-\ et
271,1976.
12. Nicolaides NJ: Fatal systemic varicella: A cases. Med J Aust 2:88-91, 1957. 13. Cheatham WJ, Weller TH, Dolan TF, et al: Varicella: Report of two fatal cases with necrop-
report of three
sy, virus isolation and serologic studies. Am J Pathol 32:1015-1035, 1956. 14. Griffith JF, Salam MV, Adams RD: The nervous system diseases associated with varicella. Acta Neurol Scand 46:279-300, 1970. 15. Heppleston JD, Pearce KM, Yates PO: Varicella encephalitis. Arch Dis Child 34:318-321, 1959. 16. Dayan AD, Stokes MI: Rapid diagnosis of encephalitis by immunofluorescent examination of cerebrospinal fluid cells. Lancet 1:177-179, 1973. 17. Sommerville RG: Rapid identification of neurotropic viruses by an immunofluorescent technique applied to cerebrospinal fluid cellular deposits. Arch Gesamte Virusforsch 19:63-69, 1966. 18. Lindeman J: M\l=u"\llerWK, Versteeg J, et al: Rapid diagnosis of meningoencephalitis, encephalitis. Neurology 24:143-148, 1974.
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Boudewijn Peters, MD; Jan Versteeg, MD; Jan Lindeman, MD; Gerard
\s=b\ In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism. (Arch Neurol 35:769-771, 1978)
Neurolatively ogical complicationschickenpox.
are rel¬ in Acute cerebellar ataxia is the most frequent of neurological syndromes in these cases, especially in children.1 No anatomicopathological correlates are available for this cerebellar syndrome since virtually all patients recover.
rare
Although an immune-mediated parainfectious or postinfectious pro¬
in varicella-associated cerebellar ataxia is assumed to be opérant, the inflammatory nature of some cases of varicella meningoencephalitis makes a single causal mechanism doubtful.2 The demonstration of varicellazoster virus antigen in the CSF of two patients with cerebellar ataxia may
cess
Accepted
for publication Jan 31, 1978. From the Departments of Neurology (Dr Peters), Neuropathology (Dr Bots), and Pathology (Dr Lindeman) and the Laboratory of Medical Microbiology (Dr Versteeg), State University, Academic Hospital, Leiden, The Netherlands. Reprint requests to Department of Neurology, State University, Academic Hospital, Leiden, The Netherlands (Dr Peters).
contribute to the
pathogenesis.
T. A. M. Bots, MD
understanding of
MATERIALS AND METHODS Antisera Antiserum to varicella-zoster virus
was
tissue in the indirect immunofluorescent test, the serum was adsorbed with liver powder and A,B, 0, and Rh antigens from human blood. The specificity and activity of the pooled serum was tested on tissue culture. No fluorescence was observed in uninfected cell cultures. Neither was any fluorescence observed in slides from cases of aseptic meningitis of other cause, for example, coxsackie virus, echovirus, and mumps. Additional controls were performed ac¬
cording to Sternberger.4 Antirabbit -globulin was prepared by immunizing goats with purified rabbit globulin. The antibody titer and the speci¬ ficity of the reaction were tested in immunodiffusion plates. After conjugation with fluorescein isothiocyanate the sera were adsorbed with liver powder and lyophilized in 1-ml aliquots. CSF Cytology and Immuno¬ fluorescent Staining Techniques The CSF
was
obtained was
The next milliliters were used for slides by means of the Sayk sedimentation technique adapted by Bots et al5 One slide was stained with MayGrünwald-Giemsa for cytologie examina¬ tion. The remaining slides were air-dried, fixed in cold acetone, and used immediate¬ ly or stored at —20 °C. Slides were treated with antisera and control sera for 60 minutes at 37 °C, washed in buffered saline pH 7.2, and subsequently treated with antirabbit conjugate for 30 minutes. After washing in phosphate-buffered sa¬ line, a drop of tris-buffered glycerine pH 9.9s was applied and the slide covered with
preparing
prepared by immunizing three rabbits with purified viral antigen mixed with Freund's complete adjuvant. The antigen used was prepared by alkaline extraction3 of in¬ fected human diploid lung fibroblasts. To overcome nonspecific binding with human
ture. The first 2 ml
investigations (blood cell count and differ¬ ential cell count, protein, glucose) by stan¬ dard laboratory procedures.
by lumbar punc¬ used for routine
a
coverglass.
Positive and negative control slides were included in the test. Fluorescence was viewed in dark-field, a high-pressure mer¬ cury lamp being used as a source of ultravi¬ olet light.
ComplementFixing Antibody Testing Paired serum samples were examined for complement-fixing antibodies against mumps, Sendai, coxsackie viruses A and B, echovirus, herpesvirus hominis, cytomegalovirus, and varicella-zoster virus. Routine laboratory investigations in¬ cluded hemogram, complete blood cell count, urinalysis, and determinations of ESR, blood glucose, BUN, creatinine, calcium, phosphorus, uric acid, total protein and albumin, cholesterol, and alkaline
phosphatase.
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Summary
of
Laboratory
Data
Virological Studies
CSF Examination
Lumbar Puncture Day 9*
Case 1 Case 2
"Day
1
Day
=
8
WBC per cu mm
15
Protein,
Cytology Viral infection Nonspecific cell irritation
mg/100 ml
19 37
IgG, mg/100 ml
1.9
Complement-Fixing Titers for Varicella-Zoster > 256 > 256
Immunofluorescent Staining CSF Cells for Virus Antigens Positive for Varicella-zoster Varicella-zoster
on
onset of rash.
Skull roentgenograms and additional EEGs were obtained in both patients.
REPORT OF CASES Case 1.—A 21-month-old boy developed a generalized vesicular exanthema, charac¬ teristic for chickenpox. The patient was afebrile. After three days the cutaneous lesions had predominantly reached the
stage of encrustation. Five days after the appearance of the rash the parents noticed spontaneous tremor-like movements of head, trunk, and arms. The next day a rapid deterioration of
gait was observed, progressing to complete inability to walk. On admission, eight days after the onset of the eruption, the boy was still afebrile. The skin showed widespread crusts. The patient was not able to stand or sit and was irritable and whimpering. The marked ataxic symptoms of trunk and extremities and the intermittent head tremor were not accompanied by other neurological abnormalities. Eight weeks after appearance of the rash the patient was
asymptomatic.
The CSF and virological investigations are summarized in the Table. On admission the complement-fixing titer against vari¬ cella-zoster virus had already reached a maximum level; no further rise could be observed. Immunofluorescence with antivaricellazoster serum by the indirect method on CSF cells was positive, showing different stages of nuclear and cytoplasmic involve¬ ment.
On cytologie examination the CSF showed a marked pleocytosis consisting of about equal numbers of monocytes and lymphocytes. A number of monocytes had cloverleaf-shaped metaplastic nuclei. The lymphoid cells showed polymor¬ phism and a remarkable basophilia of the cytoplasm. Some transitional forms to monocytes and plasma cells were seen. No macrophages were present. The metasplasia of the monocytes together with the polymorphism of the lymphoid cell series suggest a viral infection. Case 2.—Four days after the eruption of a generalized vesicular rash a 5-year-old
Positive fluorescence in CSF cells with antivaricella-zoster serum by the indirect method showing different stages of nuclear and cytoplasmatic involvement in case 1 (fluorescein isothiocyanate, 600).
boy complained of headache, accompanied with vomiting, sleepiness, and a fever of 1.6 °C; he was listless and irritable. The next day he developed a rapidly progress¬ ing gait disturbance, and his speech was noticed to be indistinct and slurred. On admission, seven days after appear¬ ance of the rash, the boy was afebrile. He was covered with crusts of various stages. The patient was noncooperative and whimpering. He was unable to sit, stand, or walk without support. A marked ataxia of trunk and extremities and a dysarthric speech completed the clinical picture. The CSF and virological studies are summarized in the table. On admission the complement-fixing titer against varicellazoster virus had already reached a maxi¬ mum level; no further rise could be observed. Indirect immunofluorescence on CSF cells with a specific antivaricella-zoster serum was positive. The insufficient quali¬ ty of the slide made for cytologie examina¬ tion of the CSF allowed only the conclusion of a nonspecific cell irritation. Results of routine laboratory tests were unremark¬ able. An EEG performed on the sixth day of admission was normal. The patient was discharged 21 days after appearance of the rash with only minimal impairment of coordination. COMMENT
The diagnosis of varicella-asso¬ ciated cerebellar ataxia in both pa-
tients was confirmed by the findings of very high titers of complementfixing antibodies in paired sera. The moderate mononuclear CSF pleiocytosis, suggesting the presence of viral infection, was confirmed by cytologie examination and by immunofluorescent staining of CSF cells with a specific antivaricella-zoster serum that showed a strong, green fluorescence, indicating different stages of nuclear and cytoplasmatic involvement (Figure). Essential data are summarized in the Table. The causative agent in varicella (chickenpox) and herpes zoster (shin¬ gles) is identical: varicella-zoster vi¬ rus. Complications of the respective diseases as they affect the CNS are
widely divergent.2 Pathogenesis in both types of CNS diseases is only partially known. In CNS disease complicating herpes zos¬
a direct viral invasion of the CNS is generally assumed.2 7S Viral isola¬ tions from brain tissue and electron microscopic demonstration of inclu¬ sions and viral particles in neurons and glia have been documented.7 In herpes zoster-associated CNS diseases the virus has been detected in CSF71" and in one case the varicellazoster antigen has been shown in CSF." In CNS complicating varicella
ter
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there are no reports of viral isolation from CNS tissue or CSF. Inclusion bodies have been observed in brain tissue in only one instance.12 Cases of fatal varicella in which there is widespread and overwhelm¬ ing infection by the varicella agent also fail to provide convincing proof of direct CNS invasion." An immunemediated process in varicella-asso¬ ciated meningoencephalitis has been postulated, based on pathological sim¬ ilarities between some cases of vari¬ cella encephalomyelitis and animals with experimental allergic encephali¬ tis.2 Griffith et al,14 in reviewing their varicella cases, stated that in virtually all instances one or another hallmark
of immune-mediated
postinfectious encephalomyelitis lacking. The pathological picture in some was
documented cases of varicella-asso¬ ciated encephalitis showed compo¬ nents, such as perivascular infiltrates, inflammatory infiltration of the leptomeninges, inclusion bodies in brain tissue, which are compatible with a direct viral invasion.1215 Therefore, evidence is lacking to postulate either a direct viral or an immune-mediated process as the single causal mecha¬ nism in varicella encephalitis or cere¬ bellar ataxia.2 To the best of our knowledge nei¬ ther the isolation of varicella-zoster virus nor the demonstration of vari¬ cella-zoster antigens in CSF cells in
of varicella-associated cerebellar ataxia (or meningoencephalitis) have been reported. Demonstration of viral antigens in CSF cells have been employed before and can be consid¬ ered as evidence for viral meningoen¬ cases
cephalitis.16"18 The data presented above appear to
constitute strong contributive evi¬ dence to assume a causal relationship between varicella cerebellar ataxia and direct viral invasion of the CNS. A definite approach to establish a direct viral invasion as the pathogenic factor would require the demonstration of varicella-zoster virus in the cerebellar
parenchyma.
References 1. Appelbaum E, Rachelson MH, Dolgopol VB: Varicella encephalitis. Am J Med 15:223-230, 1953. 2. McKendall RR, Klawans HL: Nervous system complications of varicella-zoster virus, in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam, North-Holland Publishing Co, 1978, vol 34, pp 161-184. 3. Hallauer C, and Kronauer G: Extraction of cell-associated virus without damage of the culture. Arch Gesamte Virusforsch 15:433-440, 1965. 4. Sternberger L: Immunocytochemistry. Englewood Cliffs, NJ: Prentice Hall, 1974, p 53. 5. Bots GTAM, Went LN, Schaberg A: Results of a sedimentation technique for cytology of cerebrospinal fluid. Acta Cytol 8:234-241. 1964. 6. Mrenova M, Albrecht P: Stabilization of fluorescence in preparates treated by fluorescent antibody technique. Nature 212:1256-1257, 1966.
7. McCormick WF, Rodnitzky RL, Schoket SS, al: Varicella-zoster encephalomyelitis: A morphologic and virologic study. Arch Neurol 21:559-570, 1969. 8. Hogan EL, Krigman MR: Herpes zoster myelitis: Evidence for viral invasion of spinal cord. Arch Neurol 29:309-313, 1973. 9. Gold E: Serologic and virus-isolation studies of patients with varicella or herpes-zoster infection. N Engl J Med 274:181-185, 1966. 10. Joncas J, Lussier G, Podeski MO, et al: Zoster encephalitis: A case report. Can J Public Health 59:484-486, 1968. 11. Shoji H, Koya M, Ogiwara H: Meningitis associated with herpes zoster. J Neurol 213:269\x=req-\ et
271,1976.
12. Nicolaides NJ: Fatal systemic varicella: A cases. Med J Aust 2:88-91, 1957. 13. Cheatham WJ, Weller TH, Dolan TF, et al: Varicella: Report of two fatal cases with necrop-
report of three
sy, virus isolation and serologic studies. Am J Pathol 32:1015-1035, 1956. 14. Griffith JF, Salam MV, Adams RD: The nervous system diseases associated with varicella. Acta Neurol Scand 46:279-300, 1970. 15. Heppleston JD, Pearce KM, Yates PO: Varicella encephalitis. Arch Dis Child 34:318-321, 1959. 16. Dayan AD, Stokes MI: Rapid diagnosis of encephalitis by immunofluorescent examination of cerebrospinal fluid cells. Lancet 1:177-179, 1973. 17. Sommerville RG: Rapid identification of neurotropic viruses by an immunofluorescent technique applied to cerebrospinal fluid cellular deposits. Arch Gesamte Virusforsch 19:63-69, 1966. 18. Lindeman J: M\l=u"\llerWK, Versteeg J, et al: Rapid diagnosis of meningoencephalitis, encephalitis. Neurology 24:143-148, 1974.
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