laporan kasus neuro

1. PENDAHULUAN
Hyperglycemia may initially present with neurological manifestations. Diverse
neurological symptoms have been described including: seizures, visual hallucinations,
choreoathetosis, hemiballismus dysphagia, somatosensory symptoms or headache associated
with nausea and vomiting, and severe cases of hyperglycemia can manifest as a coma.1
Epileptic seizure occur in up to 25% of cases of, non-ketotic hyperglycemia (NKH). These
seizures are the first finding of diabetes mellitus in 50% of the patients. The most common
epilepsy is known as epilepsia partialis continua (EPC), Occipital lobe seizures and aphasic
seizures may also be seen in these patients.2
Seizures related to nonketotic hyperglycemia (NKHG) have been reported with
increasing frequency since the first case documented in 1965. The clinical spectrum of this
syndrome is various with a severe course in elderly. It develops more quickly than other
disorders of diabetes mellitus with hyperglycemia, but usually without evidence of ketosis
since the syndrome often ensues during the course of any illness and yet has not been reported
in diverse medical fields, doctors must become familiar with this preventable condition,
especially in elders. Thus, only the prompt institution of appropriate insulin therapy will
improve prognosis and hasten recovery.3

2. LAPORAN KASUS
Seorang pria, 50 tahun, alamat di Kaleosan, pekerjaan petani, dibawa ke IGD tanggal
16 Oktober 2018 dengan riwayat kejang. Kejang dialami pertama kali kurang lebih 3 bulan)
dimana kejang terakhir dialami 3 hari yang lalu. Preiktal : Os sadar dan tidak mengeluh apapun.
Iktal : saat kejang kedua mata mendelik ke kiri, kepala menoleh ke kiri, mulut tidak berbusa,
lidah tergigit dan mengompol. lengan dan tungkai sebelah kiri lurus kaku. Selama kejang
pasien tidak sadar. Kejang dialami selama kurang lebih 1 menit dan berlangsung sebanyak
>20x perhari. Setelah kejang pasien sadar dan cenderung terlihat bingung. Menurut keluarga,
anggota gerak kiri pasien cenderung kurang aktif. 3 bulan terakhir ini Sebelum kejang pasien
tidak mengalami demam, cedera kepala atau nyeri kepala. Pasien belum pernah mengalami
kejang sebelumnya. Riwayat nyeri kepala kronik progresif maupun gangguan perilaku
sebelumnya disangkal. Dari riwayat penyakit sebelumnya pasien diketahui menderita penyakit
kencing manis, namun tidak rutin minum obat. Riwayat penyakit seperti hipertensi, stroke,
sakit jantung, asam urat dan sakit ginjal disangkal oleh penderita. Riwayat kebiasaan merokok
dan minum alkohol disangkal..
Pada pemeriksaan fisik didapatkan pasien dalam keadaan umum berat dengan
kesadaran somnolen. Tekanan darah 120/70 mmHg, nadi 110 x/menit, reguler, isi cukup,
frekuensi nafas 22 x/menit dan suhu badan 37,2ºC, saturasi oksigen 99%. Pada pemeriksaan
kepala tidak ada jejas. Pada pemeriksaan mata tidak terdapat konjungtiva yang anemis maupun
ikterik pada sklera. Pada pemeriksaan leher tidak ditemukan adanya krepitasi dan pembesaran
kelenjar getah bening. Pada pemeriksaan dada ditemukan suara jantung 1 dan 2 normal, tidak
ditemukan adanya bising pada jantung. Pada pemeriksaan paru-paru didapatkan ronkhi pada
kedua paru. Pada pemeriksaan abdomen ditemukan permukaan abdomen datar lemas, bising
usus normal dan tidak ada pembesaran dari hepar dan lien. Pada pemeriksaan ekstremitas, tidak
ditemukan adanya edema pada keempat ekstremitas dan akral hangat.
Pada pemeriksaan neurologis, GCS E3M6V4. Pupil bulat isokor dengan diameter
kanan dan kiri 3 mm, pupil kanan dan kiri reaktif terhadap cahaya langsung dan cahaya tidak
langsung. Pada pemeriksaan tanda rangsang meningeal tidak didapatkan adanya kaku kuduk,
laseque tungkai kanan dan kiri >70 dan kernig tungkai kanan dan kiri >135. Pada pemeriksaan
saraf kranialis nervus I tidak dapat dievaluasi, pemeriksaan N II didapatkan funduskopi ODS
papil bulat, warna jingga, batas tegas, rasio aa:vv = 2:3, tidak tampak perdarahan, kesan
normal. Didapatkan kesan paresis nervus VII kiri tipe upper motorneuron. Pemeriksaan nervus

3. III, IV, V dan VI tidak ditemukan kelainan. Pada pemeriksaan status motorik didapatkan kesan
hemiparesis kiri. Tonus otot ekstremitas kiri cenderung turun. Refleks fisiologis pada bisep,
trisep, brachioradialis, patela dan Achiles kiri menurun. Refleks patologis tidak ada hoffman
tromner dan babinski group. Tidak ditemukan klonus achiles dan klonus patela. Pemeriksaan
status sensorik tidak dapat dievaluasi. Pada pemeriksaan status otonom tidak didapatkan
adanya inkontinensia urin et alvi maupun retensio uri et alvi.
Pada pemeriksaan laboratorium tanggal 16 Oktober 2018 didapatkan kadar hemoglobin
12,2 gr/dl, leukosit 17100/mm3, eritrosit 4,52x106 /µl, hematokrit 38,7%, trombosit
423.000/mm3, gula darah sesaat 696 mg/dl, ureum 118mg/dl, kreatinin 2,1 mg/dl, natrium 119
mEq/L, kalium 2,6 mEq/L, klorida 82 mEq/L. Hasil ekspertisi EKG dalam batas normal.
Pemeriksaan x-ray thorax didapatkan gambaran cor dan pulmo kesan dalam batas normal.
Pasien dilakukan pemeriksaan ct-scan kepala polos dan didapatkan kesan gambaran lesi
hipodens bercampur dengan hiperdens di regio frontoparietal sinistra dikelilingi area hipodens
perifokal luas kesan suatu massa dengan kalsifikasi, dikelilingi perifokal edema. Pasien
didiagnosis kerja dengan status epileptikus + DM tipe 2 dengan stress hiperglikemia
Gambar 1. X-ray thorax
Penatalaksanaan dengan tirah baring, elevasi kepala setinggi 30°. Oksigen 4 liter per
menit lewat nasal kanul, mobilisasi miring kiri dan kanan tiap 2 jam, pemasangan pipa
nasogaster dan kateter urine dengan persetujuan dari keluarga. Pemasangan jalur IVFD NaCl
0.9% 500 cc per 8 jam, fenitoin loading dose 900 mg dalam NaCl 0,9% 100 cc, asam folat 400
μg tiap 24 jam Pada pasien dilakukan observasi tanda vital tiap 8 jam, direncanakan konsul
penyakit dalam untuk tatalaksana diabetes melitus tipe 2. Dari penyakit dalam pasien diberikan
novorapid 50 unit dalam NaCl 0,9% 500 cc + KN 2 500 cc/24 jam + NaCl 3% 250 cc 8 tpm
makro. Pasien direncanakan untuk rawat inap dan dikonsulkan ke divisi epilepsi. Hasil dari
perekaman EEG didapatkan kesan abnormal EEG karena adanya gelombang epileptiform yang
muncul selama 1,5 menit di sentral kanan yang bersamaan dengan postur distonik fokal sisi
kiri dimana temuan ini sesuai dengan suatu fokal epilepsy.

4. Gambar 2. CT Scan kepala tanpa kontras potongan aksial
Diagnosis
Diagnosis Klinis : Kejang fokal, paresis N.VII kiri, hemiparesis kiri
Diagnosis topis : lobus sentrotemporal kanan
Diagnosis Etiologis : Epilepsi fokal simptomatik
Diagnosis Patologis : iskemi, edema
Diagnosis tambahan : Diabetes mellitus tipe 2, Hiponatremia
Prognosis
Quo ad vitam : dubia ad malam
Quo ad fungsional : dubia ad malam
Quo ad Sanational : dubia ad malam

5. PEMBAHASAN
Nonketotic hyperglycemia (NKH) is a clinical syndrome consisting of severe
hyperglycemia, hyperosmolarity, and intracellular dehydration without ketoacidosis. The exact
incidence of HHS is not known, but it is estimated to account for ,1% of hospital admissions
in patients with diabetes (1). Most cases of HHS are seen in elderly patients with type 2
diabetes; however, it has also been reported in children and young adults. Diverse neurologic
symptoms have been described in patients with NKH, including hemichorea, seizure,
hemianopsia, and coma. Hemichorea in NKH has been attributed to petechial hemorrhage or
gemistocytic accumulation in the basal ganglia, and seizures have been associated with changes
in neuronal KATP channels or decreased neuronal levels of y-aminobutyric acid.4,11
Gambar 3. Kejang pada pasien dengan hiperglikemia7
The seizures pathogenesis caused by this disease is still controversial, as some people
think that the main pathogenesis is the lack of insulin. Among the patients, insulin levels are
sufficient to inhibit the free fatty acid metabolism and the subsequent ketoacidosis, but not
enough to transport glucose into the cells High blood glucose levels increase the levels of urine
glucose, causing osmotic diuresis effect and progressive dehydration, which would in turn
increase the incidence of this disease Some people believe that the possible mechanisms
include high blood glucose, high plasma osmolality and low γ- aminobutyric acid (GABA)
levels, and low focal cerebral ischemia. Specific mechanisms also include: (1) osmotic
changes. Hyperglycemia causes significant and rapid increase of intracellular osmotic pressure,
leading to nerve cell dehydration, and changes in enzyme activity and brain cell energy
metabolism. Membrane ion pump function is impaired, causing the loss of intracellular

6. potassium and the subsequent sodium accumulation, which destroys the membrane potential
and the stability of cell depolarization, ultimately resulting in seizures (2) in vivo biochemical
changes in metabolism. Citric acid cycle is inhibited in vivo in the patients with this disease,
whereas GABA metabolism is increased, causing the increased brain energy consumption, and
the reduced seizure threshold. In contrast, seizures are less frequent in ketoacidosis patients, as
ketosis acidosis increases intracellular activities of glutamate and tryptophan decarboxylase,
leading to the increased content of brain inhibitory neurotransmitter GABA. GABA is related
to the rapid changes of synaptic sensitivities by binding to the neurons, which then increases
the permeability of chloride ions. Under such conditions, the membrane potential is maintained
at a stable resting potential level and the excitatory synaptic reactivities are weakened so that
the epilepsy is prevented. This is also an alternative way to prove that the GABA contents
decrease in NKH-related epileptic seizures patients. (3) brain cell energy deficiency. Because
of the diabetic hyperglycemia, plasma fibrinogen significantly increases, red blood cell and
platelet aggregate, and blood is in a hypercoagulable state In addition, the aggravation of
existing diabetes microcirculation and small artery hyalinization, the dysfunction of endothelial
cells, and damages of cerebral blood flow autoregulation, decrease regional cerebral blood
flow, causing hypoxic ischemic damages and functional changes in cortical cells, which are
“epilepsy cells”. Such cells are sensitive to the metabolic disorders, high blood glucose
condition especially is likely to cause seizures (4) immune abnormalities: the presence of
glutamic acid decarboxylase autoantibodies in both type 1 diabetes and epilepsy. (5) studies
suggest that NKH related seizures might be linked to the brain barrier damage caused by long-
term high blood glucose. Early recognition of the underlying hyperosmolality is mandatory to
establish the diagnosis and to avoid the unnecessary use of prophylactic antiepileptic
medications, especially given that phenytoin can worsen the hyperglycemia4,5,6
Clinical features of NKH-related epileptic seizures: (1) common in the elderly (2) with
or without a previous history of diabetes and epilepsy (3). Seizures were always accompanied
with a rapid rise in blood glucose. Plasma osmolality may be normal or slightly elevated, but
not to the diagnostic criteria for diabetes hypertonic (4) urine ketone negative (5).Seizures
could not be effectively alleviated by antiepileptic drugs alone. Application of insulin to correct
hyperglycemia and metabolic disorders ended the seizures (6) seizure-related lesions were not
detected in the head imaging tests (7). If blood glucose was under control, epilepsy did not
occur any more.5

7. Gambar 4. Lokasi Kelainan Pada EEG pada pasien kejang dengan hiperglikemia8
The focal character of the seizures described during hyperglycemia has been reported
consistently over the years. Some authors have suggested that pre-existing or acute focal
lesions such as cortical dysplasia, heterotopia, asymptomatic strokes, and areas of
encephalomalacia from previous or acute injuries are predisposing factors for focal seizures in
patients with hyperglycemia. It has also been mentioned that focal declining in arteriolar or
venous circulation provoked by thrombosis may cause focal seizures. Glucose plays a critical
role in brain functions because it represents the main source of metabolic energy generation.
Focal motor epileptic episodes may be associated with hypoglycemia and NKH; however, these
do not occur with ketotic hyperglycemia, probably because of the anticonvulsant action of
ketosis. Most published reports on diabetic hyperglycemia are concerned with non-ketotic
hyperosmolar diabetic coma accompanied by severe hyperglycemia, hyperosmolality, and
dehydration, with minimal or no ketoacidosis, a severe condition which represents one extreme
of a biochemical continuum. In practice, actually, diabetics show a spectrum of hyperglycemia
and they are often detected before the development of severe hyperosmolarity. Although
occipital focal seizures have also been described , the clinical features of focal seizures in NKH
are usually those of frontal lobe epilepsy . The explanation of this condition by hyperglycemia
alone is unsatisfactory, because seizures are rare in diabetic ketoacidosis. It was hypothesized
that hyperglycemia leads to a decrease in epileptic seizure threshold by increasing metabolism
of GABA and accordingly decreasing the level of GABA, so resulting in a reduction in the
seizure threshold. 1,8
Singh and Strobos reported 21 patients where the first clinical manifestation was
epilepsia partialis continua. In this series almost all the patients had structural lesions. Seizure
types described in patients with hyperglycemia are diverse including epilepsia partialis

8. continua, which is the most frequent type, simple or complex partial seizures and less common
recognized symptoms are apnea, somatosensory symptoms, aphasia, and visual disturbance.
Seizures are less common in ketotic compared to non-ketotic hyperglycemia. Potential
explanation is that ketoacidosis decreases neuronal excitability by increasing levels of GABA
via activation of glutamic acid decarboxylase, increased cellular concentration of glutamic acid
and decreased GABA shunt. Other than changes in GABA, KATP channels have been recently
shown to be important in hyperglycemia-induced seizures. KATP channels are well known for
their action in pancreatic cells, where an increase in intracellular ATP/ADP ratio leads to
closure of the channels preventing potassium efflux leading to cell membrane depolarization
and insulin secretion.1,9
The modern definition and diagnostic criteria of HHS derived from case series reported
by Gerich et al. and Arieff and Carroll in 1971. They also provided insights into the
pathophysiology of the syndrome they called “hyperglycemic hyperosmolar nonketotic coma”
(HHNK). Arieff and Carroll’s diagnostic criteria included a blood glucose level .600 mg/dL, a
total serum osmolarity level .350 mOsm/L, and a serum acetone reaction from 0 to 2 pluses
when the serum was diluted 1:1 with water . Current diagnostic criteria of HHS recommended
by the American Diabetes Association (ADA) and international guidelines include a plasma
glucose level .600 mg/dL, plasma effective osmolarity .320 mOsm/L, and an absence of
significant ketoacidosis. The term HHNK was replaced with “hyperglycemic hyperosmolar
state” to reflect the fact that many patients present without significant decline in the level of
consciousness (less than one-third of patients present with coma) and because many patients
can present with mild to moderate degrees of ketosis (32,60). In some studies, up to 20% of
patients with severe hyperglycemia and hyperosmolarity were reported to have combined
features of HHS and DKA11,12,13

9. Tabel 1. Kriteria Diagnosis Hiperglikemi Hiperosmolar Non Ketotik
Once newly epileptic seizure was diagnosed, antiepileptic treatment was immediately
conducted. Intramuscular administration of phenobarbital, diazepam and valproate, or
valproate combined with carbamazepine was applied in defined cases, but with suboptimal
results. After blood glucose levels increased, insulin infusion or subcutaneous injection were
immediate applied. Close monitoring of blood glucose, saline rehydration and aggressiveness
simultaneously corrected acid-base unbalance and water and electrolyte disorders. If blood
glucose levels dropped to 8-15 mmol/L and epileptic episodes stopped, the antiepileptic drugs
would be discontinued.5
Primary treatment for the NKH-related epileptic seizures included early, active, and
rational rehydration and insulin hypoglycemic therapy, while closely monitoring blood
glucose. Such treatments are key to the success of salvage therapy among these patients.
Phenytoin-induced insulin resistance can inhibit the release of insulin, and therefore increase
the possibility of NKH-related seizures. Diazepam increase the opening frequency of GABA-
mediated chloride ion channel. Phenobarbital extended the start time of GABA-mediated
chloride channel, by reducing the brain GABA levels among the patients with NKH-related
seizures, Therefore, the stability and antiepileptic effects of phenobarbital and Diazepam
decline which explained why conventional antiepileptic drugs in those patients with epilepsy
were not marketly effective. Antiepileptic drugs preferred include carbamazepine, clonazepam
diazepam and other anti-epileptic drugs as they do not affect the levels of blood glucose. Long-
term use of anti-epileptic drugs is not necessary. If blood glucose and the seizures are well
controlled, anti-epileptic drugs can be discontinued gradually.5,10

10. Gambar 5. Tatalaksana Hiperglicemic Hyperosmolar State14

11. DAFTAR PUSTAKA
1. Afshari F, Zenteno J. Occipital Seizures Induced by Hyperglycemia : A Case
Report and Review of Literature. Elsevier.2009;382-385
2. Atmaca M, Atmaca M. Hyperglicemia Induced Non Convulsive Status
Epilepticus (NCSE) and Cranial Magnetic Resonance Imaging Results : A Case
Presentation. Turkish Epilepsy Society. Turkey. 2017;23(2);84-90
3. Younes S, Cheris Y, Aissi M, Alaya W, Beriiche O et al. Seizure and Movement
disorders induced by Hyperglicemia Without Ketosis in Elderly. Iranian Journal
of Neurology. Iran. 2014;13(3):172-176
4. Kim D, Moon Y, Noh H, Choi J, Oh J. Blood Brain Barrier Disruption is
Involved in Seizure and Hemianopsia in Nonketotic Hyperglycemia. The
Neurologist. 2011;11;17:164-166
5. Wang X. Nonketotic Hyperglicemia-Related Epileptic Seizure. Chinese
Neurosurgical Journal. China. 2017;3:16
6. Omar H, Khabiry E, Vaughan S. Seizures As The First Presentation of Diabetes
Meliitus. Sage Journals.USA. 2012(5);175-177
7. Harikrishnan B, Baburaj P, Anand R. Seizure Disorder in Diabetes: Case
Report. Kerala Medical Journal. 2016 Vol IX
8. Verroti A, Scaparrotta A, Olivieri C, Chiarelli F. Seizures and Type 1 Diabetes
Melitus : Current State of Knowledge. European Journal of Endrocinology.
Italy. 2012;167:749-758.
9. Singh BM, Strobos RJ. Epilepsia partialis continua associated with nonketotic
hyperglycemia: clinical and biochemical profile of 21 patients. Ann Neurol
1980;8:155–60.
10. Huang CW, Tsai JJ, Ou HY. Diabetic hyperglycemia is associated with the
severity of epileptic seizures in adults. Epilepsy Res. 2008;79(1):71–7.
11. Pasquel F, Umpierrez G. Hyperosmolar Hyperglicemic State : A Historic
Review of The Clinical Presentation, Diagnosis And Treatment. Diabetes Care
Journal. Atlanta. 2014 Volume 37
12. Gerich JE,Martin MM, Recant L. Clinical and metabolic characteristics of
hyperosmolar nonketotic coma. Diabetes 1971;20:228–238

12. 13. Arieff AI, Carroll HJ. Hyperosmolar nonketotic coma with hyperglycemia:
abnormalities of lipid and carbohydrate metabolism. Metabolism 1971;20:529–
538
14. Umpierrez G, Murphy M, Kitabchi A. Diabetic Ketoacidosis and
Hyperglicemic Hyperosmolar Syndrome. Diabetes Spectrum. 2002 Volume15.