1. Home>
2. Specialties>
3. Neurology>
4. Case History

A Confused Patient

A case description and diagnosis and an expert's discussion

Case Description

— T. Vythilingam Raveendran, MD, and Clive Hawkins, MD, DM

A 43-year-old woman was admitted to the hospital with a 2-month history of continuous headache. For 5 days before admission, she had increasing headache, vomiting, confusion, dizziness, and intermittent blurred vision. She also noticed, in the last 2 days, rash on her extremities. She reported a 3-week history of yellow sclera. She had no hematemesis, hemoptysis, hematuria, per-rectal bleeding, diarrhea, weight loss, frothy urine, or fever. She had had a recent chest infection with productive greenish cough. She had recently travelled to Tenerife, Spain, for vacation. She was a nonsmoker, did not use intravenous drugs, and had no contact with animals. She normally had protected sex, except on one occasion 2 months before admission. Her history included alcoholic liver disease, depression, severe pyelonephritis (7–8 years previously), recurrent cystitis, mirena coil placement, and a history of hypertension. Three pregnancies had been associated with untreated blood pressure problems.

On general examination, she was pale, jaundiced, and disoriented and had a nonblanching rash on her extremities. Her temperature was 36.2°C, pulse was 70 bpm, and blood pressure was 213/136 mm Hg. Neurological examination revealed bilateral papilledema. She had no ptosis, diplopia, ophthalmoplegia, or neck stiffness. The rest of the cranial nerve examination was normal. Examination of limbs was normal; plantar responses were flexor.

Imaging

Brain MRI was normal. Magnetic resonance venography (MRV), chest x-ray, ultrasound of renal tract, and CT of abdomen and pelvis were normal. Transvaginal ultrasound showed the IUD was satisfactorily positioned.

Hematology

The follow levels were found:

• Hemoglobin: 10.6 g/dL (6.58 mmol/L)
  
• Platelets: 90,000/µL (90 x 10 to the 9th/L)
  
• Red blood cells: 2.96 million cells/µL (2.96 x 10 to the 12th/L)
  
• Hematocrit: 0.29
  
• Lymphocytes: 1.30 x 10 to the 3rd/µL (1300 x 10 to the 6th/L)
  
• Reticulocytes: 147,000/µL (147 x 10 to the 9th/L)
  
• Erythrocyte sedimentation rate: 42 mm/hour
  

The following were normal: White blood cell count, mean cell volume, neutrophils, monocytes, eosinophils, international normalized ratio, and activated partial thromboplastin time ratio. A direct Coombs test was negative.

The blood film showed occasional fragments, normal white cells, low platelets, and platelet anisocytosis.

Biochemistry

The following were tested and found to be within normal ranges: sodium, C-reactive protein, alkaline phosphatase, corrected calcium, magnesium, phosphate, cholesterol, uric acid, creatine kinase, vitamin B12, folate, and serum cortisol.

Other findings were as follows:

• Potassium: 2.4 mEq/L (2.4 mmol/L)
  
• Urea: 51.05 mg/dL (8.5 mmol/L)
  
• Creatinine: 2.18 mg/dL (193 µmol/L)
  
• Glomerular filtration rate: 33
  
• Total bilirubin: 6.14 mg/dL (105 µmol/L)
  
• Aspartate aminotransferase: 48 U/L
  
• Gamma-glutamyltransferase: 47 U/L
  
• Lactate dehydrogenase: 527 U/L
  
• Parathyroid hormone 7: 9.3 pg/mL (0.98 pmol/L)
  
• Aldosterone/renin ratio: 67
  

Immunology

IgG, IgA, and IgM-2.0 were not elevated. The vasculitis screen was normal apart from positive P-ANCA.

Infection screen

Hepatitis B, hepatitis C, chlamydia DNA, borrelia serology, and PCR assays to detect Neisseria meningitidis and Streptococcus pneumoniae were negative. Epstein-Barr virus serology was positive; cytomegalovirus DNA copies were less than 500. Genital swabs showed absence of N. gonorrhoeae and Trichomonas vaginalis.

Urine analysis

24-hour urinary catecholamine and urine osmolality were normal. A pregnancy test was negative. Midstream urine showed raised white cell count of 275/µL. Testing for Escherichia coli was positive. Urine protein/creatinine ratio was 0.035. No Bence Jones protein was detected.

Our differential diagnosis included the following:

1. Venous sinus thrombosis, although the MRV was normal.

2. Viral or autoimmune encephalitis, but she was apyrexial.

3. CNS vasculitis, although the vasculitis screen was normal except for positive P-ANCA.

Diagnosis

We diagnosed malignant hypertension, to explain the patient's confusion and clinical picture. This was supported by blood pressure of 213/136 mm Hg on admission, bilateral papilledema, history of pregnancy-related hypertension, and family history of hypertension. Investigations were suggestive of intravascular hemolysis. Microangiopathic hemolytic anemia related to malignant hypertension can cause renal insufficiency by obstruction of interlobular arteries (Hypertension 2005; 45:246).

The patient was initially treated with nifedipine, atenolol, and furosemide. Ramipril and irbesartan were added. Her encephalopathy improved with lowering of blood pressure. After the initial improvement, the patient became confused again, associated with further rise in blood pressure. The dose of antihypertensive treatment was again increased; subsequently, the patient gradually improved clinically, without further relapse. She was discharged under the care of the renal physicians.

Discussion

— Nagagopal Venna, MD, MRCP(I), MRCP(UK)

I agree with the reporting physicians' diagnosis of malignant hypertension as the basis of the striking cerebral, renal, hepatic, and hematological dysfunction that evolved rapidly over 5 days. The presenting headache, vomiting, confusion, dizziness, and intermittent blurring of vision, although by themselves nonspecific, are characteristic of hypertensive encephalopathy. When combined with bilateral papilledema and extremely elevated blood pressure, the diagnosis becomes compelling. The lack of alternative explanations based on brain MRI supports the diagnosis. The clear initial improvement of the encephalopathy with antihypertensive treatment, the relapse when hypertension resurfaced, and its lasting resolution and subsequent sustained control make the diagnosis of hypertensive encephalopathy inescapable.

Early recognition of asymptomatic hypertension and its treatment with effective antihypertensive drugs have made this syndrome less common. The brain MRI usually reveals widespread T2 bright signals in the cerebral gyri and subcortical white matter, particularly in the occipital and parietal lobes, and sometimes in the brainstem and cerebellum. The diffusion-weighted imaging sequences are usually isointense or hypointense, indicating vasogenic edema.

In the present case, the MRI was normal. A lack of abnormality, however, does not exclude the diagnosis of hypertensive encephalopathy: The MRI changes depend on whether autoregulation in the cerebral arteriolar network has been breached. MRI changes are also less likely in individuals accustomed to chronic blood pressure elevation.

This case also illustrates the association of malignant hypertension with multiorgan damage and microangiopathic hemolytic anemia and thrombocytopenia. These conditions are caused by microvascular endothelial damage related to severe or sudden-onset hypertension. The petechiae on the limbs, easily attributable to decreased platelets, are decidedly uncommon in malignant hypertension.

In this patient, the severe hypertension could be essential hypertension or secondary to various causes. Whether renal failure is the cause or consequence of malignant hypertension is often difficult to ascertain. The presence of P-ANCA suggests that immune-mediated glomerulonephritis might be the etiology of the hypertension.

Rapid diagnosis and prompt treatment of hypertension are critical to prevent brain damage and to salvage brain function: Even severe neurological dysfunction can be reversed by such measures, and striking clearing of widespread cerebral changes is the rule. However, delays can result in seizures, coma, and death or lasting cerebral deficits (Q J Med 1979; 48:25).

The combination of this reversible clinical picture and reversible MRI changes in the posterior parts of the brain is referred to as posterior reversible encephalopathy syndrome (PRES). Most often seen with severe primary or secondary hypertension, including eclampsia, PRES is now recognized to be associated with autoimmune disorders such as systemic lupus erythematosus; transplantation of solid organ, bone marrow, or stem cells; cancer chemotherapy; and sepsis (AJNR Am J Neuroradiol 2008; 29:1036). Hypertension is present in most such cases (about 75%).

Dr. Raveendran is a Research Fellow in Neurology, Keele University Medical School, UK. Dr. Hawkins is a member of the Journal Watch Neurology Advisory Board. Dr. Venna is Director of the Neurology Clinic, Massachusetts General Hospital, and Associate Professor of Neurology, Harvard Medical School, Boston.

Published in Journal Watch Neurology November 17, 2009

Reader Remarks:

Review and add to remarks on this article

• CNS dimensions to confusional state in malignant HTN
  Douglas F Watt, Quincy Medical Center, Harvard Medical School, 18 Nov 2009 2:06 PM EST
  This is a fine case review, but it leaves out the critical question "why does malignant HTN cause a confusional... [more]
• CONFUSED PATIENT
  ANAND RV, 18 Nov 2009 2:06 PM EST
  EXCELLENT ANALYSIS AND DISCUSSION
• Differential diagnosis
  Newton Almeida, São Paulo, Brazil, 19 Nov 2009 11:44 AM EST
  Could be considered as another differential diagnosis HUS?
• MALIGNANT HBP
  JOE BARRY, PREVENTIVE MEDICINE ASSOCIATES,CAMILLUS ,NY, 19 Nov 2009 11:44 AM EST
  Rolls Royce work up for this disease high lights that we do not see it hardly ever.There needs to be... [more]
• CONFUSION,MALIGNANT HYPERTENSION
  JAYARAJAN MENON, CALICUT, KERALA,INDIA, 19 Nov 2009 11:47 AM EST
  All comprehensive appropriate differential diagnosis, and logical final diagnosis .Among the reported investigations an ECG was not seen !
• Confused Patient
  DR.RABIA AKBAR VALI, CENTRAL PRIVATE HOSPITAL, 19 Nov 2009 11:47 AM EST
  A GOOD LEARNING AND CLINICALLY APPLICABLE SUBJECT IN DAILY PRACTICE OF MEDICINE.
• Secondary causes of HTN
  O Steichen, AP-HP, Tenon Hospital, Paris, 23 Nov 2009 3:31 PM EST
  Despite high serum creatinin, serum potassium level is fairly low in this patient. I would certainly look for a secondary... [more]
• MALIG HYPERTENSION
  JOE BARRY, Camillus ,ny, 23 Nov 2009 3:35 PM EST
  Response to Douglas Watt from Harvard:.
  
  Our knowledge about brain function is still in tne dark ages. I am finishing... [more]
• TTP versus hypertensive encephalopathy
  Ragai Fouda, 24 Nov 2009 3:44 PM EST
  Dear Sir,
  
  I enjoyed reading the nicely presented case and the comprehensive discussion. I wanted to ask about the possibility... [more]
• follow-up comment to comment by Joe Barry
  Douglas F. Watt, Cambridge City Hospital, Harvard Medical School, 1 Dec 2009 1:02 PM EST
  dear Joe
  
  Thanks for your comment. I suspect that we are describing different aspects of the elephant similar to the... [more]
• hyperaldo
  RJ Beneitone, 18 Dec 2009 2:00 PM EST
  hypokalemia and raised SAC/PRA speak for Hyperaldo. Was this evaluated for?

2011 Top Stories