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also studied by Denny-Brown.2 The Hicks kindred2V6had progressive SN and SNHL but did not
appear to have a dementing illness, although "possible subnormal memory and intelligence" was
reported in one caseq2The current kindred did not
show the lancinating pains that were a prominent
symptom in the Hicks kindred2s6and in the patient
studied by Hageman et al.5 The current kindred did
not have the prominent cerebellar features that
occurred in the Portuguese kindred of Yee et a13;
these subjects had a combination of HSAN and
cerebello-olivary degeneration. The current kindred
lacked autonomic symptoms a n d h a d normal
results on detailed autonomic function testing.
The kindred reported here is of interest because
(1) hereditary SN, SNHL, and a dementing process
are linked in an autosomal dominantly inherited
disorder, and (2) the variability of expression, from
previously reported kindreds, suggests clinical
(possibly genetic) heterogeneity among kindreds
with type I hereditary SN.
From the Peripheral Neuropathy Research Center, Department of
Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN.
Supported in part by grants obtained from the National Institute of
Neurological Disorders and Stroke (NINDS 14304) and from the
Muscular Dystrophy Association (MDA).
Received August 3, 1994. Accepted in final form September 6, 1994.
In vivo proton
magnetic resonance
spectroscopy in a case
of intracranial
hydatid cyst
Address correspondence and reprint requests to Dr. Peter James Dyck,
Peripheral Neuropathy Center, Department of Neurology, Mayo Clinic,
200 First Street SW, Rochester, MN 55905.
References
1. Dyck PJ. Inherited neuronal degeneration and atrophy
affecting peripheral motor, sensory, and autonomic neurons.
In: Dyck PJ, Thomas PK, Lambert EH, eds. Peripheral neuropathy. Philadelphia: WB Saunders, 19752325-867.
2. Denny-Brown D. Hereditary sensory radicular neuropathy.
J Neurol Neurosurg Psychiatry 1951;14:237-252.
3. Yee MHC, Layzer RB, Ellis WG. Hereditary sensory neuropathy with deafness and dementia: a new syndrome
[abstract]. Neurology 1986;36(suppl 1):115.
4. Horoupian DS. Hereditary sensory neuropathy with deafness: a familial multisystem atrophy. Neurology 1989;39:
244-248.
5. Hageman G, Hilhorst BGJ, Rozeboom AR. Is there involvement of the central nervous system in hereditary sensory
radicular neuropathy? Clin Neurol Neurosurg 1992;94:49-54.
6. Hicks EP. Hereditary perforating ulcer of the foot. Lancet
1922;1:319-321.
7. Kokmen E, Smith GE, Petersen RC, Tangalos E, Ivnik RC.
The short test of mental status. Correlations with standardized psychometric testing. Arch Neurol 1991;48:725-728.
8. Dyck PJ, Kames JL, OBrien PC, Zimmerman IR. Detection
thresholds of cutaneous sensation in humans. In: Dyck PJ,
Thomas PK, Griffin J , Low PA, Poduslo JF, eds. Peripheral
neuropathy. 3rd ed. Philadelphia: WB Saunders, 1993:706-728.
9. Low PA. Autonomic nervous system function. J Clin
Neurophysiol 1993;lO:14-27.
Article abstract-We performed in vivo proton magnetic resonance spectroscopy (MRS) in a patient who had an intracranial hydatid cyst. Besides
lactate, alanine, and acetate, a large resonance for pyruvate was observed.
These findings were further confirmed by ex vivo high-resolution NMR spectroscopy of the evacuated cyst fluid, as well as of the fluid aspirated from a
cyst in the liver of the same patient. The MRS pattern appeared different
from that seen in other cystic lesions of the CNS. In vivo MRS may be used
as an adjunct to imaging in the diagnosis of intracranial hydatid cysts. It
may also have a role in monitoring drug therapy.
NEUROLOGY 1995;45:562-564
A. Kohli, MD; R.K. Gupta, MD; H. Poptani, MSc; and R. Roy, PhD
The differential diagnosis of intracranial cystic
lesions ranges from abscesses, neoplasms, and parasites to congenital cysts. Though there are suggestive features on imaging for each one of these, the
diagnosis may sometimes remain uncertain.' Since
the biochemical content of each lesion is likely to be
different, particularly with respect to amino acids
and respiratory cycle metabolites, an in vivo estimation may help to differentiate these cystic
lesions. I t was with this objective that we performed in vivo proton magnetic resonance spectroscopy (MRS) in a patient with intracranial
hydatid cyst. To the best of our knowledge, this is
the first report of in vivo proton MRS of a hydatid
cyst in a human host.
Case report. The patient was a 12-year-old boy who
562 NEUROLOGY 45 March 1995
presented with a 3-month history of headache. In the last
2 weeks preceding admission, the headache had become
severe and a mild right-sided weakness had developed.
Neurologic examination showed bilateral early papilledema and a right-sided grade 4 power with hyperreflexia
and extensor plantar response. There were no meningeal
signs, visual field deficits, parietal lobe signs, or any
other neurologic deficits. Hematologic and biochemical
investigations were normal. Cranial CT showed a large
cystic cavity in the left parieto-occipital area. A chest
radiograph a n d a n ultrasound examination of t h e
abdomen further showed a cyst in the upper lobe of the
leR lung and also in the right lobe of the liver. A clinical
diagnosis of multiple hydatid cysts was made.
MRI and spectroscopy were performed on a 2-tesla
superconducting system operating a t 1.5 tesla using a
circularly polarized head coil. T,-weighted (TRPTE =
600/15) and T2-weighted (2200/80) axial and T,-weighted
3D sagittal imaging was performed using a section thick-
A
SE 135
STEAM 20
Figure 1. TI-weightedleft parasagittal image shows a
large cyst in the parieto-occipital region causing mass
effect.
ness of 5 mm and inter-section gap of 0.5 mm for axial
imaging, a 3-mm section thickness with no inter-section
gap for sagittal images, and a 256 X 256 matrix for both
types. It revealed a large single cyst occupying almost
t h e whole of t h e left cerebral hemisphere; the cyst
appeared hypointense on TI- and hyperintense on T2weighted images and appeared to be pushing the ventricular system to the right side (figure 1).
Solvent-suppressed in vivo proton MRS was performed using s t i m u l a t e d echo acquisition mode
(STEAM)2and spin-echo (SE) sequences. An 8-ml volume
was chosen from the center of the cyst. Solvent suppression was achieved by the application of three consecutive
chemical-shift-selective pulses (60 Hz bandwidth) centered on the water resonance. Voxel homogeneity was
achieved by shimming on t h e water resonance. The
width a t half-maximum of t h e water resonance was
between 4 and 5 Hz after voxel shimming. After the
amplitudes of the saturation pulses were adjusted for
maximum solvent suppression, the spectra were obtained
from the voxel with STEAM by using TE = 20/270 msec,
TM = 29.5 msec, TR = 3,000msec, and 128 averages per
spectrum. SE sequence with TE = 135 msec, TR = 3,000
msec, and 256 averages was done to show the phase
reversal of lactate and alanine. Postprocessing of the free
induction decay was done by zero filling and gaussian
multiplication. Time domain spectra were analyzed by
Fourier transform and were phase-corrected. The real
part of the spectrum was extracted, and no baseline correction was done. STEAM 20-msec spectrum showed resonances at 1.3 ppm (assigned to lactate), 1.48 ppm (alanine), 1.92 ppm (acetate), and 2.41 ppm (pyruvate ) (figure 2A). On SE 135 msec, resonance at 1.3 ppm and 1.48
ppm showed inversion, confirming the lactate and alanine (figure 2A). The J coupling constant for methyl resonance of lactate was 7 Hz.
The complete cyst with intact membrane could be
removed on surgery, and the diagnosis was confirmed on
histologic study as Echinococcus granulosus. Fluid was
collected from the evacuated cyst and from the liver cyst,
and ex vivo high-resolution NMR was performed using a
B
+.a
3.5
1.1
2.5
2.1
1,s
I.?
.s
I1
.
.
I
Figure 2. (A) STEAM 20-msec spectrum shows
resonances at 2.41 ppm (assigned to pyruvate), 1.92 ppm
(acetate), 1.48 ppm (alanine), and 1.3 pprn (lactate). At
SE 135 msec, alanine and lactate show inversion.
(B) Single-pulse ex vivo spectrum confirms the above
assignments. (LAC = lactate, AL = alanine, AC = acetate,
P = pyruvate, TSP = sodium 3-trimethyl propionate.)
400-MHz spectrometer (Brukers, Switzerland). In each
case 450 pl of fluid was taken in a 5-mm NMR tube and
10% D20(7.5%sodium 3-trimethyl propionate [TSP])
was added to make 500 p1. A single-pulse spectrum was
obtained with a repetition time of 60 msec, a pulse angle
of 65", and 256 acquisitions. The presaturation pulse was
used for water suppression. It confirmed the assignments
seen in vivo, ie, lactate (1.3 pprn), alanine (1.48 ppm),
acetate (1.92 ppm), and pyruvate (2.41 ppm) (figure 2B).
The in vivo spectral assignment was done by placing the
methyl resonance of lactate a t 1.3 ppm, and the ex vivo
spectral assignment was done by placing the external
reference (TSP) a t 0.0 ppm. These assignments were
based on the previously reported chemical shift^.^ The
pyruvate resonance was confirmed by adding pyruvate to
the sample. The spectra from the brain and liver cyst fluids were identical.
March 1995 NEUROLOGY 46 683
Discussion. The hydatid cyst is a metabolically
active cavity. The inner lining membrane, which is
the germinal layer, is persistently generating new
smaller cysts or protoscoleces. Characteristically,
the hydatid cyst has an active glycolytic pathway
and further relies on anaerobic pathways as well as
the tricarboxylic acid cycle for energy production.
In vitro studies have shown the intermediaries of
all these metabolic pathways in the cyst contents
but particularly higher concentrations of pyruvate,
lactate, acetate, and alanine.4s5The cyst also contains a large array of amino acids, of which glycine
occurs in notable amounts. Pyruvate is present as
an end result of glycolysis and may be metabolized
via the aerobic pathway to acetate or via the anaerobic pathway to l a ~ t a t eAlanine
.~
has also been
identified as an end product of pyruvate metabolism in helminths, with glutamate acting as an
amino d o n ~ r . ~ ? ~
In the only other study we found where in vivo
and in vitro MRS was performed in the hydatid
cyst, large amounts of succinate, acetate, alanine,
creatine, glycine, and lactate were shown.3 The
study was performed on Echinococcus multilocularis cysts grown subcutaneously i n Meriones
unguiculatus. Although there was concurrence on
all other findings, we did not find succinate as
reported i n t h e above study. T h i s could be
explained on the basis of the known differences in
metabolism between E multilocularis and E granuZosus, which causes the commonly seen hydatid
cysts in the human host.4
In vivo MRS is now extensively used in the characterization of intracranial space-occupying lesions
a s well as in the study of metabolically altered
brain tissue such as infarction and epileptogenic
tissue.6 Altered tissue turnover components as well
as metabolites are the basis of tissue characterization.6 The combination of pyruvate, alanine, and
acetate was the distinctive feature of the in vivo
MRS study of the hydatid cyst. This finding also
coincides with ex vivo studies of the fluid from the
same cyst as well as fluid aspirated from another
cyst in the liver. In our experience of in vivo MRS
in more than 32 biopsy-confirmed intracranial
cysts of almost all other types, we did not record
the same distinctive combination (unpublished
data).
The present approach to t h e t r e a t m e n t of
664 NEUROLOGY 45 March 1B96
hydatid cysts aims at a sterile cyst fluid prior to
surgery. This is due to the hazards of spillage of
viable protoscoleces, with resulting toxicity and
recurrence. Albendazole, which is presently the
most effective drug, makes the protoscoleces inviable and causes structural changes in the inner
membrane.' An understanding of the metabolite
information available by in vivo MRS may make it
possible to differentiate live, degenerating, and
dead cysts and may also help in evaluating the
effect of chemotherapy.
Although t h e i n vivo a n d ex vivo r e s u l t s
appeared consistent, a single report is not sufficient to characterize t h e MRS features of t h e
hydatid cyst. Further studies in a large number of
patients may be required to substantiate the above
findings. The diagnostic and therapeutic implications appear promising.
From the Department of Neurology (Dr. Kohli) and the MR Section,
Department of Radiology (Dr. Gupta and H. Poptani), Sanjay Gandhi
Post Graduate Institute of Medical Sciences, and the Central Drug
Research Institute (Dr. Roy), Lucknow, India.
Received June 1, 1994.Accepted in final form September 7, 1994.
Address correspondence and reprint requests to Dr. Anoop Kohli,
Department of Neurology, SGPGIMS, PB 375,Lucknow 226014,India.
References
1. Sartor K. MR imaging of the skull and brain: a correlative
text atlas. Heidelberg, Germany: Springer-Verlag, 1992:630.
2. Frahm J, Merboldt KD, Hanicke W. Localized proton spectroscopy using stimulated echoes. J Magn Reson Imaging
1987;72:502-508.
3. Novak M, Hameed N, Buist R, Blackburn BJ. Metabolites of
alveolar Echinococcus as determined by 31-P and 1-H nuclear magnetic resonance spectroscopy. Parasitol Res 1992;78:
665-670.
4. McManus DP, S m y t h J D . Intermediary carbohydrate
metabolism in protoscoleces of Echinococcus granulosus
(horse and sheep strains) and E. multilocularis. Parasitology
1982;84:351-366.
5. Hurd H. Echinococcus granulosus: a comparison of free
amino acid concentration in hydatid fluid from primary and
secondary cysts and host plasma. Parasitology 1989;98:135143.
6. Howe FA, Maxwell RJ, Saunders DE, Brown MM, Griffiths
JR.Proton spectroscopy in vivo. Magn Reson Q 1993;9:31-59.
7. Gil-Grande LA, Caabeiro FR, Prieto JG, et al. Randomised
controlled trial of efficacy of albendazole in intra-abdominal
hydatid disease. Lancet 1993;342:1269-1272.