• Can differentiate obstructive, e.g. asthma, COPD, from restrictive disease, e.g. sarcoidosis, pneumoconiosis.
Pulse Oximetry
• To monitor arterial O2 saturation in patients with asthma or COPD.
pH Studies
• Ambulatory 24-hour esophageal pH monitoring is the most reliable but invasive test for GERD.
It should, therefore, be performed only after failure of empiric GERD treatment, and a negative evaluation for asthma and sinusitis.
CT Chest /MRI
• More sensitive for evaluating patients with equivocal or negative CXR findings.
• Assists in evaluating for mass lesions of neoplasms, sarcoid, ILDs, and bronchiectasis.
CT Sinus
• For diagnosing chronic sinusitis, UACS.
Table 11.2: Causes of chronic cough among adults with normal CXR
Diagnosis Differential diagnosis with normal CXR Environmental Tobacco exposure; industrial
pollutants; occupational allergens Infections— Postinfectious cough; chronic respiratory bronchitis; TB; bronchiectasis;
tropical pulmonary eosinophilia;
whooping cough
Infections/ Cerumen; Otitis media with disorders—ENT effusion; chronic sinusitis; nasal
polyp; vocal cord dysfunction/paralysis;
aspiration
Asthma Cough-variant asthma; postinfectious hyperactivity airways
Cardiac CHF; mitral stenosis GI disorders Gastroesophageal reflux
Neoplasia Bronchial adenoma; mediastinal mass with tracheal compression; laryngeal papilloma, hemangioma
Iatrogenic Drug induced; Foreign body – nose;
ear; trachea; larynx; bronchus Psychogenic Habit cough; tic cough;
psychoge-nic cough
†NAEB—a recently defined clinical entity with high eosinophilic count in induced sputum, that manifests similarly to, but is distinct from asthma in that there is neither reversible airway obstruction nor airway hypersensitivity as defined by a positive methacholine challenge.
Cough 71
Esophagogastroduodenoscopy (EGD)
• To evaluate GEDR or its complications such as esophagitis, ulceration, stricture, Barrett’s esophagus, and adenocarcinoma.
Bronchoscopy
• Generally indicated in patients with:
CT/MRI suggesting neoplasm and their biopsy procedures
Foreign body aspiration
Chronic, persistent cough with negative clinical and lab work out
Cough with hemoptysis.
Purified Protein Derivative (PPD) Skin Test
• Performed in patients with high risk of pulmonary TB. Results are read within 48 – 72 hours of placement. Test is considered positive if skin erythema measures ≥ 5 mm for HIV-infected and other immunocom-promised individuals; ≥ 10 mm for those at high risk; and ≥ 15 for all others.
HIV Serology
• In a HIV positive patient CD4+ lymphocyte count should be obtained; if it’s below 200 / mm3, a more intensive evaluation for opportunistic infection, such as PCP, TB is indicated.
Culture of Nasopharyngeal Secretions/PCR‡
• For the diagnosis of B. pertussis (Whooping cough).
Sputum Cytology
• May be helpful if history or CT/MRI suggest neoplasm.
CLINICAL NOTES
• Important historical features to be elicited are: normal (as a part of local irritation due to viral URTI) versus pathological cough;
acute versus chronic cough that persists for 3 weeks or longer; and respiratory versus nonrespiratory causes
• Generally, in patients with chronic cough, neither the patient’sdescription of his or her cough in terms of its character ortiming, nor the presence or absence of sputum production, is helpful to rule in or rule out a diagnosis or to determine theclinical approach
• Does the patient smoke – its frequency and duration; are there any occupational and environmental exposures? Is there any clear triggering or reliving factor?
• Associated red flag symptoms, including hemoptysis, weight loss, night sweats and fever, and concomitant risk factors for malignancy, HIV, and drug abuse (cocaine lung) are very significant in the evaluation of chronic cough
• Some physical signs which may provide etiological clues are: sinus tenderness (sinusitis); conjunctival injection, rhinitis (URTIs); consolidation (pneumonia); fine crackles (pulmonary edema); localized wheeze (obstructive lesion – tumor, foreign body);
cardiac – (murmur in valvular disease, S3 in CHF); ear canal – wax, hair (Arnold’s reflex)
• Ask specifically about UACS, i.e. postnasal drip, as patients often do not volunteer this information
• Although some evidence suggests that UACS is a common cause of chronic cough, it is an entity without a clear definition and no pathognomonic findings. It is usually diagnosed in the presence of suggestive symptoms such as rhinorrhea, nasal congestion, a sensation of drainage or tickle in the oropharynx, and throat clearing, with or without mucoid secretions visualized in
‡ PCR confirmation is not recommended as there is no universally accepted, validated technique for routine clinical testing.
Diagnosis: A Symptom-based Approach in Internal Medicine 72
the posterior pharynx. Its role in chronic cough, though controversial, is supported by response to therapy — usually an antihistamine-decongestant combination drug or nasal corticosteroid spray8
• Cough due to ACE inhibitors is a class effect and has been documented with all ACE inhibitors in use; changing to another agent will not ameliorate the symptoms
• A past history of recurrent lung infections from childhood is suggestive of cystic fibrosis and bronchiectasis; a history of hay fever and eczema suggests asthma; while tuberculosis, emphysema (alpha1-antitrypsin deficiency) asthma, cystic fibrosis have a familial predisposition
• In a healthy individual, cough, following URTI and persisting for at least 3 weeks, but no more than 8 weeks, consider the diagnosis of postinfectious cough. In some patients, transient bronchial hyperreactivity may be demonstrated
• In all patients with chronic cough, even in the absence of clinical signs or symptoms, consider UACS, asthma, and GERD, as they may present only as cough, and no other associated clinical findings, i.e. ‘silent’ UACS, cough-variant-asthma, and ‘silent’ GERD respectively
• In a nonsmoking patient with a clear chest radiograph who does not use ACE inhibitors, one or more of the following four causes of chronic cough account for the overwhelming majority of cases; namely, UACS, asthma, NAEB, or GERD.
RED FLAGS
• A normal lung examination does not exclude asthma, bronchitis, COPD, GERD or lung malignancy
• Failure to improve with appropriate manage ment over 4 weeks signals a need for detail work up to exclude TB, cough variant asthma, resistant pulmonary infections, malignancy, and immunosuppression
• In a patient with chronic bronchitis, any change in the character of the cough or sputum may be the presenting feature of a superimposed bronchogenic carcinoma
• Smoker’s cough should not be neglected; it may be an early symptom of bronchogenic carcinoma. Conversely, bronchogenic carcinoma is known to occur in nonsmokers or in patients with other pulmonary conditions, such as chronic bronchitis
• When a patient has a cough lasting for >2 weeks without anotherapparent cause and it is accompanied by paroxysms of coughing, posttussive vomiting, and/or an inspiratory whooping sound,the diagnosis of a B.
pertussis infection should be made unless another diagnosis is proven
• In patients with unexplained cough, evaluate the possibility of drug-induced cough.
REFERENCES
1. Senzilet LD. Pertussis is a frequent cause of prolonged cough illness in adults and adolescents.
Clin Infect Dis. 2001;32(12):1691-7. Epub 2001 May 21. [PMID: 11360208: Abstract].
2. Birkebaek NH. Bordetella pertussis in the aetiology of chronic cough in adults. Diagnostic methods and clinic.Dan Med Bull 2001;48(2):77-80. [PMID: 11414122: Abstract].
3. Tomasz J, et al. Chronic Cough From the Patient’s Perspective. Mayo Clin Proc 2007;82:56-60.
4. Kalpaklioglu AF, et al. Evaluation and impact of chronic cough: Comparison of specific vs generic quality-of-life questionnaires.Ann Allergy Asthma Immuno 2005;94(5):581-5.[PMID: 15945562:
Abstract].
5. Brignall K, et al. Quality of life and psychosocial aspects of cough. Lung. 2008; 186 Suppl 1:S55-8. Epub 2007. [PMID: 17939003: Abstract].
6. Braman SS. Postinfectious cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;
129(1 Suppl):138S-146S. [PMID: 16428703: Free full text].
7. Pratter MR, et al. Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):63S-71S.
[PMID: 16428694: Abstract].
8. O’Hara J, et al. “Postnasal drip syndrome”: Most patients with purulent nasal secretions do not complain of chronic cough.Rhinology. 2006;
44(4):270-3. [PMID: 17216744: Abstract].
SYNOPSIS
Dementia is an acquired neurological syndrome, common in the elderly, characterized by decline in memory and cognitive impairment, occurring in a state of clear consciousness (i.e. the patient is alert).
Although memory is the most common cognitive ability lost with dementia*, other common findings include (Table 12.1):1
Aphasia (i.e. difficulty with language, speech, comprehension, naming, reading, and writing);
Apraxia (i.e. difficulty with motor actions, inability to perform previously learned tasks such as combing hair, dressing);
Agnosia (i.e. difficulty with reorganization or comprehension of specific auditory, visual, and tactile stimulus); and
Impaired executive functioning (i.e. impaired planning, organization, and judgement).
Symptoms may also include changes in:
Personality (e.g. social inhibition, disinterest, explosive spells, mistrust of others, low moral character);
* Three types of memory loss may exist in demented individuals, either individually or in combination; namely:
immediate memory, i.e. difficulty in learning new information;
recent memory, i.e. recalling recent events; and remote memory, i.e. remembering past personal information.
Table 12.1: DSM-IV-TR criteria for dementia Development of multiple cognitive deficits manifested by both:
• Memory impairment (impaired ability to learn new information or to recall previously learned information) • At least one of:
Aphasia (language disturbance)
Apraxia (impaired ability to perform motor activities despite intact motor function)
Agnosia (failure to recognize or identify objects despite intact sensory function)
Disturbance in executive functioning (e.g.
planning, organizing, sequencing, abstracting) Cognitive deficits significantly interfere with work or social activities and represent major decline from previous level of functioning.
Course characterized by gradual onset and continuing cognitive decline.
Cognitive deficits not due to any of the following:
Other CNS conditions that cause progressive deficits in memory and cognition (e.g. cerebro-vascular disease, Parkinson’s disease, Huntington disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
Systemic conditions known to cause dementia (e.g. hypothyroidism, vitamin B12 and folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
Deficits do not occur only during course of delirium
Disturbance cannot be accounted for by any nonorganic mental disorder (e.g. major depressive disorder, schizophrenia)
Dementia
12
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Mood (e.g. growing apathy, depression, withdrawal, anxiety, hallucinations); and
Behavior (e.g. repetitive actions, or questioning; purposeless hyperactivity;
wandering, agitation).
These clusters of symptoms and disabilities compromise the successful performance of activities of daily living in a demented individual (e.g.
neglecting household chorus, neglecting self-care, mistakes at routine work, difficulty handling money, trouble with shopping, and difficulty in driving).
Dementia does not occur de novo, but probably represents the end of a spectrum from normal aging through an intermediate state called mild cognitive impairment (MCI - vide infra ↓↓). Early identification of MCI is important because some of the disorders that cause dementia might be treatable, reversible, and preventable (Table 12.2). On the other hand, dementia tends to be progressive, cognitive functions tend to decline steadily, vegetative symptoms such as change in appetite, weight, sleep, and fatigue are often absent, and there is little or no response to medications. The typical differentiating features between MCI and dementia✝ are given in Table 12.3.
The task of a physician caring for a demented patient, therefore, is twofold:
Early identification of those dementias that are treatable, especially because more treatment options are now available, and
Educate and support the family of the patient with incurable dementia. Much can be achieved by careful analysis of the problems, defining what can be restored and what cannot, even if the condition is irreversible.
✝ There are a variety of ‘dementias’ which most frequently are categorized as cortical or subcortical. AD is the most well-known example of a cortical dementia. Subcortical dementias include Parkinson’s, Huntington’s, and AIDS dementia. The presentation of these two types of dementias differs.
Table 12.2: Potentially treatable/reversible dementias
• Alcoholism: Chronic
• Connective tissue disorders: Temporal arteritis, vasculitis, SLE
• Drug toxicity
• Endocrine: Thyroid disease, hyperglycemia, hypo-glycemia, insulinoma, adrenal disease, pituitary disease, parathyroid disease
• Infections: Viral encephalitis, postencephalitis syndrome, chronic meningitis, AIDS, neurosyphilis
• Mass lesion: Chronic subdural hematoma (bilateral), tumor
• Metabolic: Dehydration, electrolyte disturbance, uremia, hepatic encephalopathy, hypercalcemia, hypoxia
• Normal-pressure hydrocephalus
• Nutritional: Vit. B12, folate, thiamine deficiency
• Others: Blindness, chronic seizures, CHF, dialysis encephalopathy, hearing loss, obstructive sleep apnea, radiation-induced
• Psychiatric: Depression
NOTE: Dementia due to alcoholism, HIV, TB, drugs, nutritional deficiency, and head trauma are preventable;
the rest are amicable to therapy.
Table 12.3: Typical features differentiating mild cognitive impairment and dementia Mild cognitive impairment
• Insidious onset – always
• Deficit involves memory
• Cognition remains intact
• No interference with social and occupational functioning
• May or may not eventually lead to dementia Dementia
• Insidious onset – generally
• Impaired memory and one or more of the features of aphasia, apraxia, agnosia, and impaired executive functioning
• Cognitive deficits significantly interfere with work or social activities
• Deficit represents major decline from previous level of functioning
• Deficit cannot be explained exclusively by delirium, CNS disorders, or major psychiatric illness
DIFFERENTIAL DIAGNOSIS Common
• Degenerative disorders (e.g. Alzheimer’s disease, i.e. AD; Parkinson’s disease, i.e. PD)
• Vascular dementia (i.e. VaD; e.g. multi-infarct dementia; single strategic infarct, lacunar state,
75 diffuse white matter disease, i.e. Binswanger’s
disease, hypoxic ischemic encephalopathy).
• Mixed dementia‡ (i.e. AD with VaD)2-4
• Infection (viral encephalitis, HIV-associated dementia complex/AIDS dementia complex, meningitis — TB)
• Substance abuse (alcoholism)
• Head trauma (chronic subdural hematoma, postconcussional syndrome)
• Intracranial causes (spaceoccupying lesions – tumors, abscesses).
Occasional
• Drug toxicity/polypharmacy/interactions (e.g. anticonvulsants, anticholinergics, antihistamines, antiparkinsonian, narcotics, psychotropics)5, 6
• End-organ failure (cardiac/respiratory/
hepatic/renal failure)
• Endocrine disorders (hypothyroidism)
• Neoplastic disease (primary cerebral tumors)
• Metabolic disorders (chronic electrolyte imbalance—hypocalcemia, hypercalcemia, hyponatremia, hypernatremia, hypokalemia, hepatic encephalopathy, uremia).
Rare
• Degenerative disease (e.g. dementia with Lewy bodies§, i.e. DLB; Frontotemporal dementia**, i.e. FTD; Pick’s disease; Huntington disease).
• Endocrinopathies (hyperinsulism, hyper-parathyroidism, Addison’s disease, Cushing’s syndrome, hypopituitarism)
• Autoimmune disease (cranial arteritis, SLE, MS)
• Nutritional deficiency (e.g. thiamine, B1 -Wernicke’s encephalopathy; B12, folate-pernicious anemia; nicotinic acid-pellagra)
• Chronic infections (neurosyphilis)
• Prion disease (Creutzfeldt-Jakob disease, i.e.
CJD)
• Normal pressure hydrocephalus (NPH - vide infra ↓↓)
• Hypoxic dementia (e.g. cardiac arrest, anesthetic accidents).
INVESTIGATIONS—GENERAL CBC
• To exclude anemia, including macrocytic anemia with B12 deficiency and infection.
ESR
• May be elevated in infection, inflammation, neoplasm.
Urea, Creatinine, LFTs
• Raised with renal failure.
• Increased bilirubin and transaminases with liver failure.
Electrolytes—Sodium, Potassium, Calcium, Glucose
• May be useful to monitor serum sodium and potassium in patients with dementia due to metabolic disorders.
• Hypercalcemia with hyperparathyroidism, and metastatic bone tumors.
TFTs
• An elevated TSH level with a low free T4 level is characteristic of primary hypothyroidism.
• A decreased TSH level with a high free T4 level is characteristic of primary hyperthy-roidism.
‡Mixed dementia is diagnosed when patients have evidence of AD and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions.
Growing evidence indicates that vascular dementia and AD often coexist, especially in older patients with dementia.
§A Lewy body, described by Fredrick H Lewy, is an intracytoplasmic concentrically laminated round to elongated eosinophilic inclusion which often has a dense central core surrounded by a paler peripheral rim.
**The term FTD covers both the temporal and frontal presentations of this condition: the frontal variant presents with insidious changes in personality and behavior, with neuropsychological evidence of disproportionate frontal dysfunction.
76
Neuroimaging — CT/MRI
• As a general rule, imaging should be performed in most patients with dementia.
However, it may not be warranted in patients in whom the medical history reveals no significant findings, the results of physical and neurologic examination are normal, and the onset and progression of cognitive decline are consistent with AD.
• The choice of imaging method is determined by either the patient’s condition and suspected pathologic cause at presentation or the brain region to be examined.
• CT is useful for excluding large strokes, subdural hematomas, tumor, and hydrocephalus.
• MRI is particularly recommended in patients with an atypical presentation, rapid deterioration, incontinence, focal neurologic signs, past history of head injury, or systemic diseases that prominently affect the brain (e.g. HIV infection, MS, SLE).
• New techniques including diffusion and perfusion magnetic resonance imaging are helpful for the differentiation between vascular dementia and degenerative disorders. Magnetic Resonance spectroscopy evolves as a tool for the diagnosis of different forms of degenerative dementia.
Multimodal magnetic resonance holds promise to diagnose AD at early clinical stages and to monitor the progression of the disease.7 INVESTIGATIONS—SPECIFIC Infection Screen
• Blood and urine culture may be indicated in immunocompromised patients with resistant infection.
Vitamin B12 Assay
• Vitamin B12 deficiency in megaloblastic anemia, and not infrequently found with subacute combined degeneration of the cord.
VDRL/ Fluorescein Treponema Antibody (FTA-ABS)
• Neurosyphilis—VDRL test produces false-positive result; it must be followed with a sensitive FTA-ABS test.
HIV Serology
• If the history indicates.
ANA, Anti-ds DNA
• Connective tissue disorders, such as vasculitis.
CSF
• May be indicated in those with following features:
Acute febrile episodes with meningeal signs
Atypical presentation (e.g. seizures; facial, ophthalmic, trigeminal cranial neuropathies)
Clinical findings suggestive of normal-pressure hydrocephalus
Evidence of immunosuppression
Positive serum fluorescent treponemal antibody absorption test
Suspected CJD (detection of specific 14-3-3 protein in CSF suggests CJD)
Imaging abnormalities (e.g. meningeal enhancement)
Cytology to exclude carcinomatous meningitis.