This document presents the case of a 40-year-old man admitted with altered consciousness for 3 days. His history revealed generalized aches, low back pain, decreased urine output, and weight loss over the past few months. Initial workup showed anemia, renal failure, and hypercalcemia. Imaging found an enlarged liver and vertebral fractures. Further testing identified a monoclonal band and plasma cells in bone marrow, leading to a diagnosis of multiple myeloma with hyperviscosity syndrome. He received rehydration, antibiotics, plasmapheresis, and chemotherapy.

3. Altered Sensorium
A Challenging Puzzle
BY
Dr Naseer Nazeer
Trainee Registrar
Department of
Medicine SZH

4. • `

5. HISTORY
40 years old married gentleman , resident of Sialkot
admitted through A/E on 12 th may 2015 with
presenting complain of :
Altered state of consciousness …3 days

6. HOPI
Altered state of consciousness …3 days
Insidious
Gradually worsened
Associated with headache , blurred vision and epistaxis
No H/O of any limb weakness or deviation of angle of mouth .
No H/O ocular paresis
No H/O fits , vomiting

7. Preceding history
Generalized aches and pains…3 months
Gradually worsened
partially relieved by taking NSAIDS
Aggravated by daily activities
Associated with low grade fever

8. Preceding history
 Low backache For ….2 months
Insidious in onset
Radiating to buttocks
Aggravated by sitting and walking
Relieved partially by taking injectable NSAIDS and opioids
No H/o numbness of feet
No H/o urinary retention and constipation

9. Preceding History
• H/O off and on decreased urine output …2 months
• Dysuria and Frothing in urine
• Swelling in feet
• Relieved on oral and injectable diuretic therapy
• No history of passage of stone in urine
• No history of lumbar and hypogastric pain

10. Systemic review
H/ O Weight loss (not documented )
Anorexia
Off and on H/O minor gum bleed and epistaxis
Off and on H/O low grade fever
 Dyspnea on exertion with productive cough

11. Systemic review cont
No H/o angina ,orthopnea and PND
No H/o hematemesis , melena , and alteration in bowel habits
No H/O joint pains ,swelling ,photosensitivity ,skin ulcers and
alopecia
No H/o hematuria , pyuria and lumbar pain

12. Past Medical and surgical history
History of multiple outpatient visits in vicinity
Been treated as a case of spinal TB
2 months back ATT taken for 4 weeks
No history of any surgical procedure

13. Drug history
Repeated parenteral NSAIDS and opioids
Diuretic therapy , furosemide
Allopurinol for hyperuricemia
PPI’s
No H/O any known drug allergy

14. Alive and healthy children
No history of any chronic or malignant disease in family
 Belong to Middle class
Occasional smoker
No H/O alcohol and drug abuse
No H/o intimate extramarital sexual contact
Family history
Socioeconomic and personal history

16. GPE
• Middle aged gentleman ,semi conscious and disoriented
lying on bed having GCS ..E3 V3 M6
• Vitals
BP: 110/70 mmHg
Pulse: 88 bpm
R/rate : 18 breaths per minute
Temp: Afebrile
SO2: > 90% @ room air
• Severely dehydrated and pale .

17. CNS
Pupils : Bilaterally equally reactive to light and
accommodation
Signs of meningeal irritation : Negative
Moving all limbs
Planters B/L down

18. CHEST : Normal vesicular breathing all over
PRECORDIUM: S1 and S2 no added murmur appreciated
ABDOMEN : soft , non tender
• Liver palpable (17 cm liver span)
Regular margins and smooth surface
Musculoskeletal : generalized bone tenderness but no
obvious joint swelling and deformity.

19. Initial Blood work
• Haemoglobin
• MCV
• HCT
• TLC
• PLT
• PT/APTT
parameter Patients value
Hemoglobin 5.6 g/l
Hct 15.62
ESR 160 mm/ 1st hour
MCV 83 fl
TLC 12.45 103 /microliter
PLT 32
PT-INR 1.3 sec
APTT 33 / 30
C- reactive proteins 56 mg/dl

20. Biochemical
• BUN
• CREAT
• NA
• K
• ALBUMIN
• HCO3
Uric acid
• LDH
• Total Proteins
Parameter Patient’s value
BUN 124 mg/dl
Creatinine 4.0 mg/dl
Sodium 140 mmol/l
Potassium 2.9 mmol/l
Calcium 17.2 mmol/l
Serum albumin 2.6 mg/dl
Uric acid 14.9 mg/dl
LDH 540 U/L
ALT 56 U/L
AST 45 U/L
Total proteins 12.2 g/dl

21. ABG’s

22. CT scan Brain plain
•Within normal parameters

23. Urine Analysis
Parameter Patient’s value
Specific gravity 1.020
pH Acidic
RBC’s Many
Proteins +
Glucose +
Urobilinogen +
Blood +
Casts and crystals urate crystals

24. ECG
Baseline ECG

25. Chest x ray

26. Ultrasonography
Enlarged liver with normal echogenecity
Cholelithiasis
No focal hepatic lesion or billiary dilatation
Mildly echogenic kidneys with preserved CMD
Normal spleen
No ascitis

27. Fundoscopy
• Retinal hemorrhages and exudates
• Mild disc edema

28. Differential Diagnosis
Multiple
Myeloma
Hyperviscosity
Paraproteinemia
Lymphoproliferative
dosorder
Meningoencephalitis Hyperparathyroidism
Analgesic
nephropathy
Hypercalcemia
Disseminated
Tuberculosis

29. Initial Treatment
Initial rehydration with 0.9% N/Saline @100 ml /Hour .
Passage of Nasogastric tube and foley catheter
Commencement of Broad spectrum i.v antibiotics
I.V PPIs
 Strict I/O monitoring
Vitals monitoring
Intensification of therapeutic as well as diagnostic modalities
on the basis of the initial lab work obtained

30. Further workup
Serum electrophoresis
Urine M proteins
Skeletal radiographic survey
MRI lumbosacral spine
Serum immunofixation
Bone marrow trephine

31. MRI lumbosacral spine

34. Serum electrophoresis
Atypical monoclonal band in beta region with significantly elevated titer

35. Urine M proteins
• Urine Bence jones proteins ..Negative

36. Bone marrow aspiration and trephine
• > 15% plasma cell infiltration

37. Final Diagnosis
Hyper viscosity syndrome secondary to paraproteinemia
related to multiple myeloma
 Bone Marrow Plasma cell Infiltration
 Hypercalcemia
 Renal failure
 Severe dehydration
 Vertebral compression fractures
 Diuretic induced Hypokalemia
 Hyperuricemia

38. Specific and Intensified Treatment
Consultation with hematology department for plasmapharesis
concerning Hyperviscosity related to paraproteinemia
 Laision with hematology regarding specific chaemotherapy
Three sessions of plasmapharesis with FFP’s as a
replacement fluid
While monitoring and keeping eye on other parameters

39. While at the same time
Saline diuresis continued and I.V bisphosphonates given for
hypercalcemia
Xanthine Oxidase Inhibitors for Hyperuricemia
Parenteral potassium replacement
Patient responded well to therapeutic measurers

41. WHAT is viscosity
 Viscosity is a quantity expressing the magnitude of internal
friction in fluid as measured by force per unit area resisting uniform
flow
Normal blood viscosity is < 1.8 centipoise
Hyper viscosity is abnormally thick and viscous blood
Plasma hyperviscosity(HVS) is defined as a value above the
mean +2SD limit determined for normal plasma

42. Hyper viscosity Syndrome(HVS)
Group of symptoms triggered by increase in viscosity of blood
causing impaired microcirculation ,
vascular stasis and hypoperfusion.
Hematological emergency and
can be life threatening

43. Hypervisosity syndrome
Excess cellular
component
Excess in serum
components
Polycythemia
Hyperleukocytosis
Paraproteinenemia
Cryoglobulinemia
Most common cause of hyperviscosity is hypergammaglobulinemia

44. Clinical presentation
Headache
Tinnitus / vertigo
Stupor
Coma
Gum/rectal bleed
Menorrhagia
Post surgical bleeding
Blurred vision
Cardio respiratory symptoms
Constitutional symptoms
Symptoms related to primary
disorder
Mucosal
bleeds
Impaired
vision
Neurological
features

46. Introduction
Malignant B- cell (plasma cells) proliferation derived from a
single clone .
1% of all malignancies(2% in blacks)
13 % of hematological malignancies(33% in blacks)
2500 new cases per year in UK
Median age at diagnosis is 65-70 years

47. INTRODUCTION CONT:
• Males >> females ..Blacks>> whites
• Ethnic differences , lowest incidence in Asians compared to
afro Caribbean and Caucasian population
• Radiation , benzene ,pesticide exposure and farm working etc
• Chromosomal abnormalities ..bad prognosis

48. Multiple myeloma
features
• HyperCalcemia
• Renal failure
• Anemia
• Bone pains
• Constitutional symptom
• Hyperviscosity
• Recurrent bacterial infections
Fever ,abdominal pain, Nausea ,
diaphoresis,Weight loss
Tumour burden, Osteoclastic activity
Osteoporosis, compression fractures
Hypercalcemia,Cast nephropathy
Recurrent Infections ,Renal stones
NSAID induced ,Chemotherpay
Paraproteinemia ,Hypoperfusion
Retinal artey and vein obstruction
Mucosal bleeds menorrhagia
Hypogammaglobulinemia
Chemotherapy related
Marrow infiltration
Cytopenias
Altered mental status,
Confusion, depression
Weakness ,Dehydration
Kidney stones
C
R
A
B

49. Myeloma related organ damage
• Elevated calcium levels
• Renal insufficiency
• Bone marrow infilteration
• Bone lesions
• Hyperviscosity
• Amyloidosis
• Recurrent bacterial infections

50. Multiple myeloma
staging

51. Prognostic criteria

52. Management
General
Aspects
Combination
chemotherapy
Stem cell
transplant

53. General Aspects
i. Analgesia
ii. Monitor renal function
iii. Local radiotherapy
iv. Spinal support
i. High fluid input
ii. Rapid treatment of hypercalcemia
iii. Caution with nephrotoxic drugs
iv. Chemotherapy
i. Bisphosphonates
ii. Hydration
iii. Loop diuretics
i. Xanthine oxidase inhibitors
i. Local radiothearpy
ii. Fixation of fracture
iii. Bisphosphonate prohylaxis
Pain control
Renal impairment
Hypercalcemia
Hyperuricemia
Bone disease
Recurrent Bacterial infections
Require Anitbiotics
paraproteinemia
Plasmapharesis ,
Primary disorder

54. Specific Management
• Variable regime chemotherapeutic options
• Stage and extent dependant
• Possibility and availability of curative stem cell
transplant

56. THANK YOU!!