S336 19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
defecation, excessive sweating and heat intolerance. Two days
prior to presentation, she suddenly stopped walking. Examination
revealed a young woman with fever of 38.5, bilatral proptosis and
pitting pedal edema. She had goitre with warm sweaty palms and
fine tremors. Power was grade 1 in all the limbs. The deep tendon
reflexes were exaggerated with sustained ankle clonus. She had
bilateral proptosis, lid lag and lateral rectus palsy. The pulse rate was
144beats/min. The blood pressure was 170/50. Potassium level was
2mmols/L. An assesment of thyrotoxic periodic paralysis was made.
She improved remarkably after rehydration. Power increased to
grade 4 with mainly proximal myopathy. While being investigated,
she went into premature labour and developed thyroid storm. She
died in labour ward.
Conclusion: Thyrotoxic hypokalemic periodic paralysis is unusual
in the African woman. The diagnosis and management of such a
patient present great challenges in a resource poor setting.
PO33-FR-07
Centropontine myelinolysis and hypokalemia
I. Ben Hamouda1, M.N. Tougourti2, D. Mohsen2, M. Hamza2.1Neurology, Charles Nicolle Hospital, Tunis, Tunisia; 2Medicine, Razi
Hospital-La Manouba, Manouba, Tunisia
Purpose: Centropontine myelinolysis is a rare but severe anatomo-
clinical entity. Fast normalisation of severe hyponatremia has long
been considered as the main cause of this injury. Hypokalemia has
rarely been implicated in the pathogenesis of this disease. We report
a centropontine myelinolysis case with chronic and permanent
hypokalemia.
Observation: A 42 years old woman is hospitalized for numbness
and weakness in the lower limbs. Medical history: mild hypothy-
roidism and Sjogren’s syndrome, diagnosed a few years ago, initially
presented as a tubular nephritis with permanent hypokaliemia.
Renal function and natremia were normal. On admission, she
was alert and had tetrapyramidal syndrome. Cranial nerves were
preserved. Biological investigation showed a severe hypokalemia
(2.6mmol/l). Cerebral MRI disclosed a central pontine hypersignal
T2 suggestive of myelinolysis. Angio MRI excluded active vasculitis.
Discussion: Central pontine myelinolysis, once a merely anatomic
diagnosis, is currently easier to diagnose. In our opinion, fast
normalisation of hyponatremia should no longer be considered as
its main cause, as many other conditions have been implicated in its
aetiology, such as alcoholism, anorexia nervosa, chronic renal and
liver diseases. Chronic hypokalemia is presumably the cause of pon-
tine injury in our patient. Six other similar cases have been reported
in the literature. In some of them, hpokalemia was of acute onset
and transitory. In one observation, hypokalemia was secondary to a
tubular nephritis in the setting of Sjogren’s syndrome, like our case.
The mechanism of the pontine injury is unknown. Some hypotheses
are proposed referring to cellular injuries described in some
pathological conditions and presumably caused by hypokalemia.
Conclusion: The increasingly available neuroimaging techniques
enable an easier diagnosis of centropontine myelinolysis, which
clinical presentation, treatment and prevention are linked to its
different etiologies.
PO33-FR-08
Hyponatraemia – role of high environmental temperature
and salt intake
P. Sanchetee. Sanchetee Neurology Research Institute, Jodhpur, India
Purpose: Hyponatraemia, defined as serum sodium concentration
less than 135 mEq/L, is the commonest electrolyte abnormality
seen in neurocritical care. Risk factors include extremes of age,
postoperative, malignancy, pulmonary disease, pharmacological
agents, and patients with brain injury or infection. Aim of this
presentation is to document hyponatraemia in the setting of
restriction in salt intake, use of diuretics and routine use of
hypotonic fluids in hot climate.
Methods: Observational study over a period of 15 months of
23 patients presented with severe hyponatraemia and with
encephalopathy complicating acute neurological presentation.
Results: There were 14 male and 9 female patients in age range
of 33 years to 71 years. Underlying disorders were stroke (6),
CNS infections (4), status epilepticus (3), head injury (3), primary
hyponatraemia and miscellaneous (7). Associated factors were
restriction of salt intake (16) and use of diuretics (9), use of
hypotonic intravenous fluid replacement (11), high environmental
temperature (15) and no cause evident in 3 patients. Clinical
presentation was nonspecific and included altered sensorium, ab-
normal behavior, seizures, fever, and bradycardia. While 7 patients
died and 5 were severe disabled, 10 patients made good clinical
recovery. Prognostic factors were underlying disorder, coma at
onset, advancing age, and duration and severity of hyponatraemia.
Conclusions: Hyponatraemia is a common following acute
neurological insult. There is need to re-evaluate the practice of
salt restriction and use of diuretics in patients with hypertension
in regions with high ambient temperature. Awareness and early
treatment can decrease risk of death and length of hospital stay.
PO33-FR-09
Case series of hyperglycemia presenting as fit or funny
movements
P. Alagia Nambi1, V. Karthikeyan2, M. Dhiviya3,
P. Namasivayam Balamurugan3, R. Thamilselvi4. 1Medicine,
Sri Gokulam Hospital, Salem, India; 2Nephrology, Sri Gokulam
Hospital, Salem, India; 3Neurology, Sri Gokulam Hospital, Salem,
India; 4Sri Gokulam Hospital, Salem, India
Nonketotic Hyperosmolar Hyperglycemia (NKHH) is characterized
by extreme hyperglycemia, increased osmolarity and severe
dehydration without significant Ketosis or acidosis. We report a
case series of NKHH presenting as either recurrent focal seizures
or abnormal movements.
A total of 7 patients were documented by video recording over 3
yrs. All presented as focal seizures or abnormal movements and
all were fully conscious either during (n =4) or in between attacks
(n = 3). Table 1 shows their biochemical profile compared with
typical DKA and NKHH. In all CT brain were normal and their EEG
showed either focal or generalized slowing or sharp waves.
Our patients were between classical DKA and NKHH in terms of
their blood biochemistry but clinically they had the following
typical prototype: Highly recurrent seizures or episodes of
movements 20–50/day. Normal Neuro Imaging and all were
symptom free with fluid and insulin therapy. Early recognition
of neurological manifestation of non ketotic hyperglycemia can
prevent the mortality associated with these syndromes.
PO33-FR-10
Impaired mitochondrial energy metabolism and neuronal
apoptotic cell death after chronic aluminum exposure in rat
brain
P.O.O. Khanna, B.I.M. Nehru. Dept of Biophysics, Panjab University,
Chandigarh, India
The present study elucidates a possible mechanism by which
chronic aluminum exposure (100mg/kg b.wt. p.o. for 8 weeks
daily) causes neuronal degeneration. Mitochondria, the primary
site of cellular energy generation and oxygen consumption might
represent a likely target for aluminum toxicity. Therefore, the
objective of the current study was to investigate the effect of chronic
aluminum exposure on mitochondrial energy metabolism, oxidative
stress generation and its implication in the induction of neuronal
apoptosis in rat model. Mitochondrial fractions were isolated from
cerebral cortex, mid brain and cerebellar region of rat brain and
the complexes were estimated biochemicaly in the same fractions.
Our results indicated significant decrease in the activity of complex
I, II and IV in all the three regions, though the changes were more
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339 S337
pronounced in mid brain region. The MTT assay which indirectly
shows the activity of complex III did not register any significant
change except for mid brain. Mitochondria generate ROS that are
thought to augment intracellular oxidative stress. The alterations in
the mitochondrial electron transfer enzyme activities in turn might
have caused an increase in malondialdehyde which is observed
in all the three regions. Further the decreased levels of GSH and
also decreased MnSOD activity in the mitochondrial fraction of rat
brain enhanced oxidative stress. Thus, chronic aluminum exposure
increases the oxidative stress both by mitochondrial damage as
well as due to the failure in the ROS removal system which in
turn causes oligonucleosomal DNA fragmentation and formation
of comet, a hallmark of apoptosis. The present study provides an
evidence of impaired mitochondrial bioenergetics and apoptotic
neuronal degeneration after chronic exposure of aluminum.
PO33-FR-11
Protective role of lithium during aluminium-induced
alterations in rat brain
P. Bhalla, M.L. Garg, D.K. Dhawan. Department of Biophysics, Panjab
University, Chandigarh, India
The present study was conducted to assess the role of lithium in
aluminium toxic conditions. To carry out the various investigations,
Al was administered at a dose of 100mg/kg b.wt./day whereas
lithium was supplemented in diet (1.1 g/kg diet, daily) for the
period of two months. Ca2+ ATPase activity was observed to be
decreased in Al treated animals. Whereas, a significant increase in
Ca2+ influx and in the levels of cAMP were observed following Al
treatment which were decreased with lithium co-administration.
Further, a significant increase in the levels of phospholipase C
(PLCyI) was observed following Al treatment which was normalized
following lithium supplementation. The nitric oxide synthase
enzyme activity and the levels of L-citrulline were also found to
be significantly increased in cerebrum and cerebellum after Al
treatment, which were significantly decreased following lithium
supplementation. The DNA damage caused in the cell as a result
of Al treatment was examined by single cell gel electrophoresis
as well as DNA fragmentation studies and a significant increase
in the DNA damage was observed which was found to be
significantly improved upon lithium supplementation. Alterations
in the neuronal histoarchitecture and ultra structure were also
observed following Al treatment. Lithium supplementation greatly
restored normalcy in the cerebrum and cerebellum layers with
no loss of cerebral or purkinje cell layer as evident by light
microscopy. Further, lithium supplementation to Al treated rats
resulted in appreciably thwarting the ultrastructural changes with
regard to integrity of the cells as a whole as well as the cell
organelles as observed by transmission electron microscopy. The
study demonstrates that lithium, has the potential in containing
or reversing the Al-induced functional and structural changes as
evidenced by oxidative stress, DNA damage and altered calcium
homeostasis as well as disordered signal cascade.
PO33-FR-12
Sialidosis and malignancy: the possible relationship between
the abnormal metabolism of sialitic acid and malignancy from
a family of genetically defined sialidosis
T. Kobayashi1, Y. Yagi1, A. Machida1, S. Touru1, T. Uchihara2.1Neurology, Nakano General Hospital, Tokyo, Japan; 2Neurology, Tokyo
Metropolitan Institute for Neuroscience, Tokyo, Japan
Purpose: To investigate the possible relationship between the
abnormal metabolism of sialitic acid and malignancy from a family
of genetically defined sialidosis.
Methods: Clinical and pathological studies of three siblings of
the family of sialidosis type I carrying V217M/G243R mutations
in sialidase gene.
Results: All three siblings (elder and younger sisters, and brother)
were biochemically identified marked sialidase deficiency. The
genetical analysis was performed from cultured fibroblasts of
the elder sister (Naganawa et al., 2000). The clinical onsets of
their sialidosis were ataxic gaits or incidentally identified macular
cherry-red spot around age 15. Their clinical symptoms had been
gradually worse with painful convulsive attacks, action myoclonus
and impairment of walking, but their intelligence were normal.
The elder sister suffered from colon cancer at age 45. And the
younger sister suffered from ovarian tumor at age 37. The brother
suffered from malignant lymphoma of diffuse B cell type at age 30,
which was refractory to multiple courses of standard (CHOP)
and intensified (ESHAP) chemotherapy and local irradiation for
palliation.
Discussions and Conclusions: Association of malignancy (malig-
nant lymphoma, colon cancer, and ovarian tumor) has not been
described in the literature and could be by chance. However, a
series of evidence suggests a possible link between sialidase/sialic
acid and malignancy (Miyagi et al., 2004). It is interesting that
less expression of sialidase in some cell lines of colon carcinoma
is related to their highly metastatic nature relative to cell lines
expressing more abundant sialidase (Sawada et al, 2002). It is also
reported that the presence of sialitic acid in the surface of diffuse
large B cell lymphoma is associated with shorter survival (Suzuki
et al, 2003). So this family provides a quite valuable information of
investigating between malignancy and sialidase deficiency/sialitic
acid metabolism.
PO33-FR-13
Inhibitory effect of tyrphostin AG126 on brain synaptosomal
dysfunction induced by cholesterol oxidation products
D.E. Kim1, C.K. Ha2, S.H. Park3, J.K. Roh4. 1Neurology, Seoul Veterans
Hospital, Seoul, Republic of Korea; 2Neurology, Inha University
Hospital, Incheon, Republic of Korea; 3Neurology, Seoul National
University Bundang Hospital, Bundang, Republic of Korea; 4Neurology,
Seoul National University Hospital, Seoul, Republic of Korea
Background: Formation of cholesterol oxidation products is a
suggested mechanism of neurodegenerative disorders. Neuronal
cell death is mediated by an increased release of excitotoxic gluta-
mate from the presynaptic nerve endings. Tyrosine-specific protein
kinases modulate neurotransmitter release at the nerve terminals.
Tyrphostin AG126 has anti-inflammatory and cytoprotective effects.
However, it remains uncertain whether tyrphostin AG126 has an
effect preventing alteration of nerve terminal function induced by
the cholesterol oxidation products.
Methods: The present study was performed to assess the effect
of cholesterol oxidation products against nerve terminal function
using synaptosomes isolated from rat cerebrum. We determined
the preventive effect of tyrphostin AG126 against oxysteroltoxicity
by measuring the effects on the glutamate release, depolarization
of membrane potential, changes in Ca2+ levels, and Na+/K+-ATPase
activity.
Results: Synaptosomes treated with 7-ketocholesterol or 25-
hydroxycholesterol exhibited a sustained release of glutamate,
depolarization of membrane potential, early rapid increase in
cellular Ca2+ levels and decrease in Na+/K+-ATPase activity. Those
responses were concentration-dependent. Treatment of tyrphostin
AG126 interfered with alteration of synaptosomal functions and
decrease in Na+/K+-ATPase activity induced by 7-ketocholesterol or
25-hydroxycholesterol.
Conclusions: The results show that 7-ketocholesterol and 25-
hydroxycholesterol seem to cause the release of glutamate by
inducing depolarization of membrane potential and early rapid
increase in cellular Ca2+ levels and by inactivating Na+/K+-ATPase
in the cerebral synaptosomes. Treatment of tyrphostin AG126 may
prevent the oxysterol-induced nerve terminal dysfunction.