What is the diagnosis and treatment for a patient with new daily persistent headache?

New Daily Persistent Headache: Diagnosis and Treatment

Immediate Diagnostic Priority

The first critical step is to rule out spontaneous intracranial hypotension (SIH), as new daily persistent headache with an initial orthostatic quality is a key presenting feature of this treatable secondary cause. 1

Red Flag Assessment

Before diagnosing primary NDPH, exclude secondary causes by evaluating for:

• Orthostatic features: Headache absent or mild (1-3/10) on waking, onset within 2 hours of becoming upright, >50% improvement within 2 hours of lying flat 1
• Thunderclap onset followed by persistent headache (consider subarachnoid hemorrhage or SIH) 1
• Progressive worsening or headache awakening patient from sleep 2, 3
• Focal neurological deficits or headache worsening with Valsalva maneuver 2, 3

Diagnostic Workup for Suspected SIH

If orthostatic features are present:

• Brain MRI without and with IV contrast to identify venous sinus engorgement, pachymeningeal enhancement, midbrain descent, or subdural collections 1
• Spine MRI without and with IV contrast to localize CSF leak source via epidural fluid collections or dilated epidural venous plexus 1
• Note that CSF pressure can be normal in SIH patients, so normal opening pressure does not exclude the diagnosis 1

Differential Diagnosis Beyond SIH

Once secondary causes are excluded, distinguish NDPH from:

• Chronic migraine: Provoked by movement rather than posture, with established migrainous biology including aura, nausea, photophobia 1
• Postural tachycardia syndrome (PoTS): Documented heart rate increase >30 bpm on standing tests 1
• Cervicogenic headache: Provoked by cervical movement, reduced cervical range of motion, myofascial tenderness 1

Diagnostic Criteria for Primary NDPH

NDPH is diagnosed when the patient can pinpoint the exact date of headache onset, with continuous unremitting pain developing within 24 hours and persisting without remission. 4

Key features:

• Sudden onset with patient able to recall the specific day headache began 4, 5
• Continuous daily headache from onset, lacking remission 4, 5
• Variable phenotype: May present with migraine-like features (throbbing, photophobia, nausea) or tension-type features 4, 5
• Prevalence: 0.03-0.1% in general population, higher in children and adolescents 4

Treatment Strategy

First-Line Pharmacologic Treatment

Treat NDPH based on the predominant headache phenotype, as there are no controlled trials specifically for NDPH. 4, 5

For Migraine-Like NDPH Phenotype:

CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) should be considered first-line, given emerging evidence of complete remission in migraine-like NDPH. 6, 7

• Erenumab 70-140 mg subcutaneous monthly has demonstrated complete resolution in case reports of NDPH with migraine features 6
• These agents reduce migraine days by 2-4.8 days per month with favorable tolerability 8
• Monitor blood pressure with erenumab due to postmarketing warnings for hypertension development 8

Topiramate 50-100 mg daily is an alternative first-line option with the strongest evidence base for chronic migraine prevention 1, 8

• Start at 25 mg daily, titrate slowly to 100-200 mg in divided doses 1, 8
• Common adverse effects: cognitive slowing, paresthesias, weight loss, kidney stones 1, 8
• Full benefit may take 2-3 months to manifest 8

For Tension-Type NDPH Phenotype:

Amitriptyline is the drug of first choice for tension-type headache prophylaxis 3

• Particularly beneficial if comorbid depression or sleep disturbances present 2, 3
• Adverse effects: dry mouth, sedation, weight gain, constipation 2

Second-Line and Refractory Treatment Options

For patients not responding to phenotype-based treatment:

OnabotulinumtoxinA demonstrates efficacy in approximately 34.5% of NDPH patients, with 59% reporting patient-perceived improvement 9

• Two treatment cycles recommended before assessing response 9
• Favorable safety profile with no serious adverse events 9

Intravenous ketamine or lidocaine for refractory cases 5

Nerve blockade appears more efficacious in children than adults 5, 7

Trigger-Specific Treatments

If infectious trigger suspected: Consider antiviral medications and neuroinflammation-targeting treatments 5

If headache started with thunderclap or Valsalva: Consider CSF-lowering medications 5

If concurrent affective disorders: SSRIs, SNRIs, or benzodiazepines may provide benefit 5

Non-Pharmacologic Interventions

Implement for all patients:

• Dietary modifications: Reduce caffeine and alcohol consumption 5
• Sleep hygiene optimization 5
• Cognitive-behavioral therapy (CBT) and biofeedback 2
• Regular aerobic exercise 2, 3

Monitoring and Follow-Up

• Headache diary to track frequency, severity, triggers, and medication use 2, 3
• Evaluate treatment response at 2-3 months after initiating or changing preventive therapy 8, 2
• Monitor for medication overuse headache: Limit triptans/ergots to <10 days/month and simple analgesics to <15 days/month 8
• Refer to headache specialist if no improvement or diagnostic uncertainty 3

Critical Pitfalls to Avoid

• Do not miss SIH: Always assess for orthostatic features, as this is a treatable secondary cause masquerading as NDPH 1
• Do not abandon treatment prematurely: Full benefit of preventive therapy requires 2-3 months 8
• Do not use valproate in women of childbearing age due to teratogenic effects 3
• Recognize treatment refractoriness: NDPH is one of the most treatment-refractory primary headache disorders; even aggressive treatment is often ineffective 4, 5