CURRICULUM VITAE

Nama : Henhen Heryaman,dr.,SpPD

TTL : Garut, 17 November 1975
Agama : Islam
Jabatan Fungsional : Dosen Fakultas Kedokteran
Akademik Universitas Padjadjaran
Perguruan Tinggi : Fakultas Kedokteran Universitas
Padjadjaran (UNPAD)
 RIWAYAT PENDIDIKAN
Tahun Lulus Program Pendidikan Institusi
1994 SMA SMAN 1 Garut
2004 Dokter FK Unpad
2014 Spesialis 1 FK Unpad
 PENGALAMAN MENGAJAR
Program Institusi/Jurusan/Progr Sem/Tahun
Mata Kuliah
Pendidikan am Studi Akademik
Biokimia Sarjana FK Unpad
Kedokteran
Ilmu Penyakit Dalam D3 Poltekes Kebidanan 2013-2015
Kebidanan Bandung
METABOLIC
ENCEPHALOPATHY(ME)
HENHEN HERYAMAN
RANI W. PRASANTI
SMF ILMU PENYAKIT DALAM
RS BHAYANGKARA TK 1I SARTIKA ASIH
BANDUNG
LEARNING OBJECTIVE:

• DEFINITION OF ME
• PATHOPHYSIOLOGY OF ME
• CLINICAL MANIFESTASION OF ME
• SPECIFIC ETIOLOGIES OF ME
• TREATMENT OF ME
LEARNING OBJECTIVE:
• DEFINITION OF ME
• PATHOPHYSIOLOGY OF ME
• SPECIFIC ETIOLOGIES OF ME
• CLINICAL MANIFESTASION
• TREATMEN OF ME
• Metabolic encephalopathy is defined as a potentially reversible abnormality of
brain function caused by processes of extracerebral origin
• Confusion is clinically defined as the inability to maintain a coherent stream of
thought or action.
• Delirium is a confusional state with superimposed hyperactivity of the
sympathetic limb of the autonomic nervous system with consequent signs
including tremor, tachycardia, diaphoresis, and mydriasis.
• Acute toxic-metabolic encephalopathy (TME), which encompasses
delirium and the acute confusional state, is an acute condition of
global cerebral dysfunction in the absence of primary structural brain
disease
• TME is common among critically ill patients.
• Furthermore, TME is probably under-recognized and undertreated,
especially when it occurs in patients who require mechanical
ventilation
• TME is usually a consequence of systemic illness, and the causes of TME
are diverse.
• Most TME is reversible, making prompt recognition and treatment
important.
• Certain metabolic encephalopathies, including those caused by
sustained hypoglycemia and thiamine deficiency (Wernicke’s
encephalopathy), may result in permanent structural brain damage if
untreated.
• Alcohol withdrawal syndromes must be excluded in patients with
suspected TME.
 LEARNING OBJECTIVE:

• DEFINITION OF ME
• PATHOPHYSIOLOGY OF ME
• CLINICAL MANIFESTASION OF ME
• SPECIFIC ETIOLOGY OF ME
• TREATMENT OF ME
 LEARNING OBJECTIVE:

• DEFINITION OF ME
• PATHOPHYSIOLOGY OF ME
• CLINICAL MANIFESTASION OF ME
• SPECIFIC ETIOLOGY OF ME
• TREATMENT OF ME
• Normal neuronal activity requires a balanced environment of
electrolytes, water, amino acids, excitatory and inhibitory
neurotransmitters, and metabolic substrates
• normal blood flow, normal temperature, normal osmolality, and
physiologic pH are required for optimal central nervous system
function
• Complex systems, including those mediating arousal and awareness
and those involved in higher cognitive functions, are more likely to
malfunction when the local milieu is deranged
• All forms of acute TME interfere with the function of the ascending
reticular activating system and/or its projections to the cerebral
cortex, leading to impairment of arousal and/or awareness
• Ultimately, the neurophysiologic mechanisms of TME include
interruption of polysynaptic pathways and altered excitatory-
inhibitory amino acid balance
• The pathophysiology of TME varies according to the underlying
etiology
 HEPATIC ENCEPHALOPATY (HE)

• CHARACTERIZED :
• ALTERATION COGNITION
• MOTOR FUNCTION
• CONSCIOUSNESS

• COMPLICATION OF LIVER CIRRHOSIS

• ACUTE LIVER FAILURE
• THREE TYPES OF HE
• TYPE A : ACUTE LIVER FAILURE
• TYPE B : PORTO-SYTEMIC SHUNTS IN ABSENCE OF LIVER DYSFUNGTION
• TYPE C : LIVER CIRRHOSIS
 HEPATIC ENCEPHALOPATY (HE)
• GRADING :
• HE 1 : ATTENTION DEFICITS AND PSYCOMOTOR SLOWING
• HE II: LETAHARGY AND DISORENTATION
• HE III : SOMNOLENCE AND SEMI-STUPOR
• HE IV : COMA
• WITH OR WITHOUT: EXTRAPYRAMIDAL, PYRAMIDAL AND CEREBELLAR SIGN
• MOST CHARACTERISTICS ARE HYPOMIMIA, HYPOKINESIA, RIGOR, TREMOR, DYSARTIA,
DYSDIADOCHOKINESIA AND ATAXIA .
• HYPERREFLEXIA AND POSITIVE PYRAMIDAL SIGN ( III AND IV)
• ASTERIXIS (II AND III)
Butterworth et al. (2018)
 HEPATIC ENCEPHALOPATY (HE)

• DIAGNOSIS
• EXCLUDE OF OTHER POSSIBLE CAUSES OF BRAIN DYSFUNCTION
• RESOLVE WITH HE THERAPY
• DD/ WERNICKE’S ENCEPHALOPHATY
• TOOLS :
• PSE-SYNDROME TEST
• CRITICAL FLICKER FREQUENCY (CFF)
• EEG

VILSTRUP et al.2014
 Butterworth et al. (2018)
Journal of Liver and Clinical Research

LOLA AND HE IN CIRRHOSIS

• 370 patients with cirrhosis and bouts of OHE were screened. After exclusion, 193 (52.16%)
patients were randomized to receive either intravenous infusions of LOLA (n = 98), 30 g daily, or
placebo (n = 95) for 5 days. Standard of care treatment (including lactulose and ceftriaxone) was
given in both groups
• The grade of OHE was significantly lower in the LOLA group (compared to placebo) on days 1-4
but not on day 5

Sidhu et al 2017. Hepatology Journal

 UREMIC ENCEPHALOPATHY

• ACCUMULATE GUANIDINO COMPOUNDS DUE TO RENAL DYSFUNCTION

• INTERFERE WITH GLUTAMATERGIC; GABA-ERGIC NEUROTRANSMISSION
• INCREASES NEURONAL CALCIUM LEVEL AND NEUROEXICTATION (SECONDARY
HYPER-PT)
 UREMIC ENCEPHALOPATHY

• CLINICAL SYMTOMS :
• EMOTIONAL ALTERATION : DEPRESSION, SLIGHT ATTENTION MEMORY DEFICITE,
ALTERATION CONSCIOUSNES.
• COGNITION ALTERATION : CONFUSION, PHYSICOSIS, SEIZURE AND COMA
• HYPERREFLEXIA
• ASTERIXIS
• TREMOR
• MYOCLONUS
 UREMIC ENCEPHALOPATHY

• MANAGEMENT
• HEMODIALYSIS
• THIAMINE SUPPLEMENTATION
• KETOANALOGS SUPPLEMENTATION
SUBJECT SELECTION
KETOANALOUGS SUPPLEMENTATION

Che-Hsiung Wu et al 2017 PLoS ONE 12(5): e0176847.

Che-Hsiung Wu et al 2017 PLoS ONE 12(5): e0176847.
 HYPOGLICEMIA

• DD/; FOCAL NEUROLOGICAL SYMPTOMS IN ACUTE OR SUBACUTE ONSET

• SEVERE HYPOGLICEMIA : SPEECH ARREST, HEMIPARESIS OR HEMICHOREA
• MOST COMMON OCCURS : ADO, (SOLFUNILUREA) INSULIN
• MEDICAL EMERGENCY
2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia

HYPOGLICEMIA

Neurogenic (autonomic) Neuroglycopenic

Trembling Difficulty Concentrating

Palpitations Confusion

Sweating Weakness

Anxiety Drowsiness

Hunger Vision Changes

Nausea Difficulty Speaking

Dizziness
2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia

Risk factors for severe hypoglycemia in people treated with sulfonylureas or insulin

•Prior episode of severe hypoglycemia

•Current low A1C (<6.0%)
•Hypoglycemia unawareness
•Long duration of insulin therapy
•Autonomic neuropathy
•Chronic kidney disease
•Low economic status, food insecurity
•Low health literacy
•Preschool-age children unable to detect and/or treat mild hypoglycemia on their own
•Adolescence
•Pregnancy
•Elderly
•Cognitive impairment
2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia

SEVERITY OF HYPOGLICEMIA
• Mild
– Autonomic symptoms present
– Individual is able to self-treat

• Moderate
– Autonomic and neuroglycopenic symptoms
– Individual is able to self-treat

• Severe
– Requires the assistance of another person
– Unconsciousness may occur
– Plasma glucose is typically <2.8 mmol/L
2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia

TREATMENT SEVERE HYPOGLICEMIA

UNCONSCIOUS PERSON WITH IV ACCESS
1. Treat with 10-25 g (20-50 mL of D50W) of glucose intravenously over 1-3 minutes

2. Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat with a further 15 g of carbohydrate if
needed

3. Once conscious, eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus
protein
 HYPERGLICEMIA

• HYPERGLICEMIA EMERGENCIES :
 DKA
 HHS

• ALTERATION CONCIOUSNESS, SEIZURE AND FOCAL NEUROLOGICAL DEFICITES

• STROKE MIGHT ACCOMPANY HSS
• ASSOCIATED INFLAMATORY AND PROCOAGULANT STATE
• PARTIAL EPILEPSIA AND HEMICHOREA
MANAGEMENT OF CHRISIS HYPERGLICEMIA

Abbas et al 2018: care.diabetesjournals.org

 CONCLUSION

• ETIOLOGY OF ME STILL UNCLEAR

• HYPOGLYCEMIA COMMON CAUSES OF SU AND INSULIN
• CRISIS HYPERGLYCEMIA INDUCES STROKE (HSS)
• LOLA DECREASES GRADING OF HE
• KETOANALOGS DECRESES FREQUENCY OF HD AND DEATH