Prolonged confusion in Hepatic patient

Usama Ragab
Usama RagabLecturer of Medicine at Zagazig Faculty of Medicine em Zagazig University
Case
Presentation
By
Usama Ragab Yousif
MSc. Internal Medicine
• 73-year old male patient, Gameel
Mohamad Abdo, from Zagazig, Married
and have 3 offspring the youngest is 25
years old, retired, has no special habits of
medical importance and is right handed
Personal History
• Disturbed conscious level 20 days before.
Complaint
History of Present Illness
A known hypertensive, HCV +ve patient with
confusion started 3 weeks ago with acute onset to
which he was admitted to near ER, blood sugar was
measured and was low, he received 200 cc of
D25W, he rapidly gained his consciousness and was
discharged with no specific plan.
The condition occurred again 3 days later to which
he received same treatment in home.
They sought medical advice, admitted to a private
hospital with recurrent attacks of hypoglycemia.
He received continuous infusion of D10W.
Investigations were done:
CBC: 5.6/12.8/89
RFT: creatinine=0.8 mg/dL, urea=21 mg/dL
LFT:
•Bilirubin= 0.7 mg/dL
•Albumin= 3.6 g/dL, T.protein= 6.2 g/dL
•ALT/AST= 93/109 (N= up to 40 U/L)
INR: 1.01
History of Present Illness (cont.)
Cortisol (PM): >250 ng/mL (N= 24.61-171.52 ng/mL)
Thyroid functions: T4=89.61 (N=60-120 nmol/L)
TSH=2.84 (0.45-4.5)
Fasting insulin levels: 11.8 µIU/mL (N= 0.7-9 µIU/mL)
C-peptide: normal
Pelviabdominal US: Cirrhotic liver changes with
splenomegaly (15.5 cm)
History of Present Illness (cont.)
History of Present Illness (cont.)
The patient still have repeated hypoglyecemic
attacks and was discharged for further work up, then
he was admitted to medical ICU in Zagazig
university Hospitals.
Past History
Diseases:
•Hypertension of 10 years duration on irregular
treatment.
•HCV +ve 10 years duration on non specific
treatment.
Operations: prostatectomy was done 1 year ago
due to cancer prostate with no chemotherapy,
radiotherapy or hormonal treatemnt.
Drugs: liver support, irregular treatment with
antihypertensive medications
Family History
No similar conditions in the family
No positive consanguinity between both parents
Appearance: looks ill and irritable
Built: average
Complexion: no pallor, no cyanosis, no jaundice, no
pigmentation
Decubitus: lies flat on bed
Facial Expression: no characteristic facies
General Examination
Head & Neck examination:
•Eyes: no pallor, no cyanosi, no jaundice, normal
eye brows and lashes
•Hair: normal
•Nose: normal
•Lips: no pallor, no cyanosis, no signs of
vitamins deficiency
•Parotid: not enlarged
•LN and thyroid: not palpable
•Neck veins: pulsating, no congested.
General Examination (cont.)
Extremities:
• Upper limbs: no clubbing, no pigmentations,
no pallor, normal muscles and nerves.
• Lower limbs: bilateral lower limb edema up to
knees, no pigmentation, scar of old burn on the
lateral side of the right thigh.
Back: no pigmentation, no swelling, no spine
deformities.
General Examination (cont.)
Cardiac examination
Inspection/Palpation: no precordial bulge, no
pulsation, apex is normaly located in 5th space MCL,
regular rate 100/min, no dullness outside the apex,
no thrill, no palpable sounds
Percussion: normal percussion notes
Auscultation: normal heart sounds, no additional
sound, no murmur
Examination (cont.)
Chest examination:
Inspection/Palpation: symmetrical chest, no bulge,
no retraction, no visible veins, no pulsation, no
deformity, normal TVF bilaterally.
Percussion: resonant except bare area of the heart.
Auscultation: normal vesicular breathing, no
additional sounds (no crackles, no rhonchi,
bronchophony or aegophony.
Examination (cont.)
Examination (cont.)
Abdomenal examination
Inspection: distended abdomen with full flanks bil
aterally, visible viens, wide subcostal angle, midline
scar of prostatectomy, everted umbilicus, normal h
air distribution, no pigmentation, no hernial orifice
s, as regard genitalia; no deformity, mild scrotal sw
elling
Palpation: no rigidity, no tenderness, liver is palpa
ble 4 fingers in MCL & 6 fingers in midline which i
s firm to hard in consistency, spleen is palpable 3 f
ingers below costal margin, no plapable paraaortic
LN, no pulsation
Percussion: shifting dullness bilaterally
Auscultation: normal intestinal sound, no bruit or
venous hum.
Neurological examination
Mentality: patient is comatose.
Cranial nerve examination:
•Olfactory: cannot be assessed
•Optic: cannot be assessed
•3,4 & 6th Cr.N.: cannot be assessed except for
intact light reflex
•7th: normal facial symmetry, no mouth deviation,
no drooling of saliva.
•8th: cannot be assessed
•9,10,11th: normal gag reflex.
General Examination (cont.)
Neurological examination
(cont.)
Sensory: cannot be assessed
Motor:
•Tone: normal.
•Power: cannot be assessed
•Reflexes: normal
Cerebellar: cannot be assessed
Gait: cannot be assessed
General Examination (cont.)
CBC: 6/11.5/147
Bil (T/D): 1.79/1.39
Alb/TP: 2.8/5.5
ALT/AST: 30/504
Cr: 0.7
BUN: 7.2
INR: 1.1
Investigations
PSA: 0.36 (N)
B.hCG: <0.01 (N)
Investigations (cont.)
AFP: 35019 IU/mL !!!
PAUS: Cirrhotic liver with mild splenomegaly (15.5
cm) & bilateral renal gravel.
CT brian was done because confusion was
prolonged: NAD
MRI brain: SOL for metastatic workup, in
periventricular area, surrounded by toxic edema for
further evaluation and clinical and histopathologic
correlation.
CT abdomen & chest (multislices): normal chest,
cirrhotic liver + splenomegaly.
Investigations (cont.)
•Continuous IV infusion of D10W.
•Antiencephalopathy measures.
•Antibiotics.
•Nursing care and care of comatose
patient.
•Fluid balance.
Treatment
Differential Diagnosis
Ellul, M. A., et al. (2015). Hepatic encephalopathy due to liver cirrhosis. BMJ (Clinical research ed.), 351, h4187.
Differential Diagnosis
From PE Cryer et al: J Clin Endocrinol Metab 94:709, 2009. ©The Endocrine Society, 2009.
Brain metastasis
Of
primary HCC
The 10 Most Commonly Diagnosed Cancers: 2012 Estimates
Total Number and Percentage of New Cases Diagnosed per Year, Worldwide
Bowel including anus ICD-10 C18-C21
Please include the citation provided in our Frequently Asked Questions when reproducing this chart: http://info.cancerresearchuk.org/cancerstats/faqs/#How
Prepared by Cancer Research UK
Original data sources:
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide:
IARC CancerBase No. 11 [Internet].Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 16/01/2014.
Also, Int. J. Cancer: 136, E359–E386 (2015)
Cancer as a leading cause of death
worldwide
1) Lung cancer (19% of all cancer deaths; 1.6 million people).
2) Liver cancer (9% of all cancer deaths; 745,000 people).
3) Stomach cancer (9% of all cancer deaths; 723,000 people).
4) Colorectal cancer (9% of all cancer deaths; 694,000 people).
5) Breast cancer (6% of all cancer deaths; 522,000 people).
Int. J. Cancer: 136, E359–E386 (2015)
Is it common for HCC to
metastasize to brain?
Brain metastases from hepatocellular carcinoma are
extremely rare.
Brain metastases from HCC are being increasingly
documented in areas of the world with high endemic
rates such as Asia.
Lung metastasis is the chief site of extrahepatic
metastasis, followed by regional and distant lymph
nodes, musculoskeletal system, adrenal glands,
kidneys and bone marrow.1
1- Radiology 2000; 216:698–703 & World J Surg 2008, 32:2213-2217. & Cancer 2011;117:4475–83.
Is it common for HCC to
metastasize to brain?
 Brain metastases from HCC seem be observed more
frequently due to prolonged survival, improvements in
modern neuroimaging modalities that can detect small
metastases in asymptomatic patients.
 Commonly, other extrahepatic sites are co-affected in
the same setting, mainly, lung and bone.
Radiology 2000; 216:698–703
Journal of Neuro-Oncology (2006) 76: 93–98
Jiang et al. BMC Cancer 2012, 12:49
Intracranial metastasis was found in only 1 case, a
liver-cell tumor that also involved the pituitary gland.
In 1 case electroencephalographic evidence of a focal
lesion suggested intracerebral metastasis but
postmortem examination of the brain was not
permitted.
Cancer. 1964 Jun 1;17(6):757-68.
Some of the reported cases of HCC with brain
metastasisReview of literature
PresentationAuthority
2 cases of cerebral metastasisPatton et al. (1964)
7 cases of cerebral metastasis from primary hepatomaChang & Chen
(1979)
9 cases with brain metastasis (1989, over 28 years)Shuangshoti et al.
16 cases of hepatoma presenting as craniospinal metastasis
without obvious hepatic involvement
Lee (1992)
2 cases with cerebral metastasis as first presentationLoo et al. (1994)
18 cases with brain metastasisYen et al. (1995)
7 patients with brain metastasisKim et al. (1998)
Brain metastasis after hepatectomy for HCC.Moriya et al. (1999)
Brain metastasis seen after hepatectomy in 5 casesAsahara et al. (1999)
45 cases with Intracranial metastasis from primary HCCChang et al. (2004)
62 patients were found to have brain metastasesChoi et al. (2009)
41 case with brain metastasisJiang et al. (2012)
World J Gastroenterol 2004;10(11):1688-1689 Surg Neurol 62: 172–177, 2004
Jiang et al. BMC Cancer 2012, 12:49
Characteristics of BM from primary HCC
Choi et al. Journal of neuro-oncology, 91(3), 307-313.
Characteristics of BM from primary HCC
Ok… is it really rare?
• The improvement in patient survival following wide
variety of curative options such as successful liver
transplantation, liver resection together with
advancement of new methods, such as
percutaneous ethanol injection (PEI) and
transarterial chemoemobolization also,
improvement in chemotherapy option (multikinase
inhibitor).
Gastroenterology 127(Suppl. 1):S218–S224.
Final bottom line
• Common is common, but rare is not always rare.
• Think beyond the liver (and put brain in your
mind).
• Your patients are living more now (or expected
to be), don’t rush them to the grave.
Prolonged confusion in Hepatic patient
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Prolonged confusion in Hepatic patient

  • 2. • 73-year old male patient, Gameel Mohamad Abdo, from Zagazig, Married and have 3 offspring the youngest is 25 years old, retired, has no special habits of medical importance and is right handed Personal History
  • 3. • Disturbed conscious level 20 days before. Complaint
  • 4. History of Present Illness A known hypertensive, HCV +ve patient with confusion started 3 weeks ago with acute onset to which he was admitted to near ER, blood sugar was measured and was low, he received 200 cc of D25W, he rapidly gained his consciousness and was discharged with no specific plan. The condition occurred again 3 days later to which he received same treatment in home. They sought medical advice, admitted to a private hospital with recurrent attacks of hypoglycemia. He received continuous infusion of D10W.
  • 5. Investigations were done: CBC: 5.6/12.8/89 RFT: creatinine=0.8 mg/dL, urea=21 mg/dL LFT: •Bilirubin= 0.7 mg/dL •Albumin= 3.6 g/dL, T.protein= 6.2 g/dL •ALT/AST= 93/109 (N= up to 40 U/L) INR: 1.01 History of Present Illness (cont.)
  • 6. Cortisol (PM): >250 ng/mL (N= 24.61-171.52 ng/mL) Thyroid functions: T4=89.61 (N=60-120 nmol/L) TSH=2.84 (0.45-4.5) Fasting insulin levels: 11.8 µIU/mL (N= 0.7-9 µIU/mL) C-peptide: normal Pelviabdominal US: Cirrhotic liver changes with splenomegaly (15.5 cm) History of Present Illness (cont.)
  • 7. History of Present Illness (cont.) The patient still have repeated hypoglyecemic attacks and was discharged for further work up, then he was admitted to medical ICU in Zagazig university Hospitals.
  • 8. Past History Diseases: •Hypertension of 10 years duration on irregular treatment. •HCV +ve 10 years duration on non specific treatment. Operations: prostatectomy was done 1 year ago due to cancer prostate with no chemotherapy, radiotherapy or hormonal treatemnt. Drugs: liver support, irregular treatment with antihypertensive medications
  • 9. Family History No similar conditions in the family No positive consanguinity between both parents
  • 10. Appearance: looks ill and irritable Built: average Complexion: no pallor, no cyanosis, no jaundice, no pigmentation Decubitus: lies flat on bed Facial Expression: no characteristic facies General Examination
  • 11. Head & Neck examination: •Eyes: no pallor, no cyanosi, no jaundice, normal eye brows and lashes •Hair: normal •Nose: normal •Lips: no pallor, no cyanosis, no signs of vitamins deficiency •Parotid: not enlarged •LN and thyroid: not palpable •Neck veins: pulsating, no congested. General Examination (cont.)
  • 12. Extremities: • Upper limbs: no clubbing, no pigmentations, no pallor, normal muscles and nerves. • Lower limbs: bilateral lower limb edema up to knees, no pigmentation, scar of old burn on the lateral side of the right thigh. Back: no pigmentation, no swelling, no spine deformities. General Examination (cont.)
  • 13. Cardiac examination Inspection/Palpation: no precordial bulge, no pulsation, apex is normaly located in 5th space MCL, regular rate 100/min, no dullness outside the apex, no thrill, no palpable sounds Percussion: normal percussion notes Auscultation: normal heart sounds, no additional sound, no murmur Examination (cont.)
  • 14. Chest examination: Inspection/Palpation: symmetrical chest, no bulge, no retraction, no visible veins, no pulsation, no deformity, normal TVF bilaterally. Percussion: resonant except bare area of the heart. Auscultation: normal vesicular breathing, no additional sounds (no crackles, no rhonchi, bronchophony or aegophony. Examination (cont.)
  • 15. Examination (cont.) Abdomenal examination Inspection: distended abdomen with full flanks bil aterally, visible viens, wide subcostal angle, midline scar of prostatectomy, everted umbilicus, normal h air distribution, no pigmentation, no hernial orifice s, as regard genitalia; no deformity, mild scrotal sw elling Palpation: no rigidity, no tenderness, liver is palpa ble 4 fingers in MCL & 6 fingers in midline which i s firm to hard in consistency, spleen is palpable 3 f ingers below costal margin, no plapable paraaortic LN, no pulsation Percussion: shifting dullness bilaterally Auscultation: normal intestinal sound, no bruit or venous hum.
  • 16. Neurological examination Mentality: patient is comatose. Cranial nerve examination: •Olfactory: cannot be assessed •Optic: cannot be assessed •3,4 & 6th Cr.N.: cannot be assessed except for intact light reflex •7th: normal facial symmetry, no mouth deviation, no drooling of saliva. •8th: cannot be assessed •9,10,11th: normal gag reflex. General Examination (cont.)
  • 17. Neurological examination (cont.) Sensory: cannot be assessed Motor: •Tone: normal. •Power: cannot be assessed •Reflexes: normal Cerebellar: cannot be assessed Gait: cannot be assessed General Examination (cont.)
  • 18. CBC: 6/11.5/147 Bil (T/D): 1.79/1.39 Alb/TP: 2.8/5.5 ALT/AST: 30/504 Cr: 0.7 BUN: 7.2 INR: 1.1 Investigations
  • 19. PSA: 0.36 (N) B.hCG: <0.01 (N) Investigations (cont.) AFP: 35019 IU/mL !!!
  • 20. PAUS: Cirrhotic liver with mild splenomegaly (15.5 cm) & bilateral renal gravel. CT brian was done because confusion was prolonged: NAD MRI brain: SOL for metastatic workup, in periventricular area, surrounded by toxic edema for further evaluation and clinical and histopathologic correlation. CT abdomen & chest (multislices): normal chest, cirrhotic liver + splenomegaly. Investigations (cont.)
  • 21. •Continuous IV infusion of D10W. •Antiencephalopathy measures. •Antibiotics. •Nursing care and care of comatose patient. •Fluid balance. Treatment
  • 22. Differential Diagnosis Ellul, M. A., et al. (2015). Hepatic encephalopathy due to liver cirrhosis. BMJ (Clinical research ed.), 351, h4187.
  • 23. Differential Diagnosis From PE Cryer et al: J Clin Endocrinol Metab 94:709, 2009. ©The Endocrine Society, 2009.
  • 25. The 10 Most Commonly Diagnosed Cancers: 2012 Estimates Total Number and Percentage of New Cases Diagnosed per Year, Worldwide Bowel including anus ICD-10 C18-C21 Please include the citation provided in our Frequently Asked Questions when reproducing this chart: http://info.cancerresearchuk.org/cancerstats/faqs/#How Prepared by Cancer Research UK Original data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet].Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 16/01/2014. Also, Int. J. Cancer: 136, E359–E386 (2015)
  • 26. Cancer as a leading cause of death worldwide 1) Lung cancer (19% of all cancer deaths; 1.6 million people). 2) Liver cancer (9% of all cancer deaths; 745,000 people). 3) Stomach cancer (9% of all cancer deaths; 723,000 people). 4) Colorectal cancer (9% of all cancer deaths; 694,000 people). 5) Breast cancer (6% of all cancer deaths; 522,000 people). Int. J. Cancer: 136, E359–E386 (2015)
  • 27. Is it common for HCC to metastasize to brain? Brain metastases from hepatocellular carcinoma are extremely rare. Brain metastases from HCC are being increasingly documented in areas of the world with high endemic rates such as Asia. Lung metastasis is the chief site of extrahepatic metastasis, followed by regional and distant lymph nodes, musculoskeletal system, adrenal glands, kidneys and bone marrow.1 1- Radiology 2000; 216:698–703 & World J Surg 2008, 32:2213-2217. & Cancer 2011;117:4475–83.
  • 28. Is it common for HCC to metastasize to brain?  Brain metastases from HCC seem be observed more frequently due to prolonged survival, improvements in modern neuroimaging modalities that can detect small metastases in asymptomatic patients.  Commonly, other extrahepatic sites are co-affected in the same setting, mainly, lung and bone. Radiology 2000; 216:698–703 Journal of Neuro-Oncology (2006) 76: 93–98 Jiang et al. BMC Cancer 2012, 12:49
  • 29. Intracranial metastasis was found in only 1 case, a liver-cell tumor that also involved the pituitary gland. In 1 case electroencephalographic evidence of a focal lesion suggested intracerebral metastasis but postmortem examination of the brain was not permitted. Cancer. 1964 Jun 1;17(6):757-68.
  • 30. Some of the reported cases of HCC with brain metastasisReview of literature PresentationAuthority 2 cases of cerebral metastasisPatton et al. (1964) 7 cases of cerebral metastasis from primary hepatomaChang & Chen (1979) 9 cases with brain metastasis (1989, over 28 years)Shuangshoti et al. 16 cases of hepatoma presenting as craniospinal metastasis without obvious hepatic involvement Lee (1992) 2 cases with cerebral metastasis as first presentationLoo et al. (1994) 18 cases with brain metastasisYen et al. (1995) 7 patients with brain metastasisKim et al. (1998) Brain metastasis after hepatectomy for HCC.Moriya et al. (1999) Brain metastasis seen after hepatectomy in 5 casesAsahara et al. (1999) 45 cases with Intracranial metastasis from primary HCCChang et al. (2004) 62 patients were found to have brain metastasesChoi et al. (2009) 41 case with brain metastasisJiang et al. (2012) World J Gastroenterol 2004;10(11):1688-1689 Surg Neurol 62: 172–177, 2004
  • 31. Jiang et al. BMC Cancer 2012, 12:49 Characteristics of BM from primary HCC
  • 32. Choi et al. Journal of neuro-oncology, 91(3), 307-313. Characteristics of BM from primary HCC
  • 33. Ok… is it really rare? • The improvement in patient survival following wide variety of curative options such as successful liver transplantation, liver resection together with advancement of new methods, such as percutaneous ethanol injection (PEI) and transarterial chemoemobolization also, improvement in chemotherapy option (multikinase inhibitor). Gastroenterology 127(Suppl. 1):S218–S224.
  • 34. Final bottom line • Common is common, but rare is not always rare. • Think beyond the liver (and put brain in your mind). • Your patients are living more now (or expected to be), don’t rush them to the grave.